Granted Patent
B2
US 12,594,281 · App. 19/210,898 · Granted Apr 7, 2026
Pharmaceutical dosage forms and methods of use
Inventors:
Stephen P. Wanaski (Chicago, IL); Virginia D. Schmith (Cocoa Beach, FL); Jay A. White (Newmarket, CA); Timothy M. Cunniff (Chicago, IL)
Assignee:
EMALEX BIOSCIENCES, INC.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Pharmaceutical dosage forms of D1/D5 receptor antagonists, and related methods of their use, are disclosed.
Claims (30)
1 . A pharmaceutical dosage form for intra-oral absorption of ecopipam, comprising ecopipam or a pharmaceutically acceptable salt thereof and a pH modifier, the pH modifier being present in amount such that the pharmaceutical dosage form has a pH of about 2 to about 4, wherein when the dosage form is in solid form, the pH is as measured after dissolving the dosage form in 30 g of artificial saliva having a pH of 6.72, wherein the pH modifier comprises one or more of citric acid, hydrochloric acid, ascorbic acid, and acetic acid or a salt thereof.
2 . The pharmaceutical dosage form of claim 1 , comprising ecopipam HCl.
3 . The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form comprises about 0.01 to about 0.8 wt % pH modifier based on the total weight of the formulation.
4 . The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form has a pH of about 2 to about 3.5.
5 . The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form is a tablet, powder, sachet, film, gel, gum, aerosol, oral lyophilizate, oravescent, sprayable liquid, wafer, mouthwash, or lozenge.
6 . The pharmaceutical dosage form of claim 5 , wherein the tablet is an orally dissolvable tablet, a fast-dissolving tablet, a buccal tablet, or a sublingual tablet, or wherein the film is a bioadhesive film, mucoadhesive film, or bucco adhesive film.
7 . The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form comprise one or more excipients selected from the group an absorption enhancer (also called permeation enhancer), an antioxidant, a binder, a carrier, a colorant, a diluent, a disintegrant, a flavor, a lubricant, a pH modifier, a plasticizer, a preservative, a sweetener, a taste masking agent, a taste modulating agent, a viscosity modifier, a lyophilization agent, and nitrosamine scavengers, and including one or more from each group of excipients.
8 . The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form comprises an absorption enhancer selected from one or more in the group of chelators; nonionic surfactants; cationic surfactants; anionic surfactants; fatty acids; non-surfactants; enzymes, chitosan, trimethyl chitosan, poly-l-arginine, l-lysine, chondroitinase ABC, 1-dodecylazacycloheptan-2-one, and quillajasaponin.
9 . The pharmaceutical dosage form of claim 1 , wherein upon administration, the pharmaceutical dosage form reduces a pH of saliva of a subject by at least 1 pH unit.
10 . The pharmaceutical dosage form of claim 1 , wherein upon administration, the pharmaceutical dosage form reduces a pH of saliva of a subject to 6.5 or less, 6 or less, 5.5 or less, 5 or less, 4.5 or less, or 4 or less.
11 . The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form comprises one or more compounds selected from AB block copolymers of oligo(methyl methacrylate) and PAA, acacia, and polyvinyl alcohol, anionic types, Carbopol e.g. 934P, cationic types, chitosan, copolymers of PAA and PEG monoethylether monomethacrylate, epoxy resins, Eudragit polymers, gelatin, gellan gum, glycol, guar gum, hyaluronic acid, hydrogels of poly(N N-dimethylaminoethyl methacrylate-co-methyl methacrylate), hydrophilic pressure-sensitive adhesives (PSAs), hydroxyethyl cellulose, hydroxyethyl methacrylate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, a modified starch-polyacrylic acid mixture, monomeric alpha-cyanoacrylate, PAA complexed with PEGylated drug conjugate, pectin, poly(acrylic acid/divinyl benzene), polyacrylates, polymethacrylates, polycarbophil, polyethylene carboxymethyl cellulose, polymers with thiol groups, polymethyl vinyl ether-maleic anhydride, polystyrenes, polyurethanes, polyvinyl pyrrolidone, psyllium amberlite-200 resin, sodium alginate, sodium alginate, tamarind gum, thermally modified starch, tragacanth, and xanthan gum.
12 . The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form comprises an amount of ecopipam or a pharmaceutically acceptable salt thereof, of about 1 wt % to about 40 wt % based on the total weight of the pharmaceutical dosage form.
13 . The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form comprises an amount of ecopipam or a pharmaceutically acceptable salt thereof, of about 1 mg to about 200 mg.
14 . A method of improving a safety profile of ecopipam, comprising administering to a subject in need thereof the pharmaceutical dosage form of claim 1 , wherein the ecopipam is intraorally absorbed, wherein the safety profile is improved as compared to an oral dosage form of ecopipam or pharmaceutically acceptable salt in which ecopipam is absorbed in the GI tract.
15 . The method of claim 14 , wherein the improved safety profile is improved cardiac safety.
16 . The method of claim 15 , wherein administering the pharmaceutical dosage form reduces risk of QT prolongation.
17 . A method of reducing one or more first pass metabolite concentrations in plasma when administering to a subject in need thereof the pharmaceutical dosage form of claim 1 for intraoral absorption of the ecopipam, wherein the one or more first pass metabolite concentrations are reduced after administration of the pharmaceutical dosage from as compared to after administration of an oral dosage form of ecopipam or pharmaceutically acceptable salt in which ecopipam is absorbed in the GI tract.
18 . The method of claim 17 , wherein the one or more first pass metabolites comprises ecopipam glucuronide.
19 . The method of claim 18 , wherein a concentration of ecopipam glucuronide is reduced by 75% to 85% after administration of the pharmaceutical dosage form as compared to a concentration of ecopipam glucuronide after administration of the oral dosage form.
20 . The method of claim 17 , wherein the first pass metabolites comprise EBS-101-40853 and/or EBS-101-40853 glucuronide.
21 . The method of claim 20 , wherein a concentration of EBS-101-40853 is reduced by 48% to 55% after administration of the pharmaceutical dosage form as compared to a concentration of EBS-101-40853 after administration of the oral dosage form and/or wherein a concentration of EBS-101-40853 glucuronide is reduced by 60% to 76% after administration of the pharmaceutical dosage form as compared to a concentration of EBS-101-40853 glucuronide after administration of the oral dosage form.
22 . A method of administering a pharmaceutical dosage form of claim 1 to a subject in need thereof with a UGT inhibitor, or on a dosing schedule that overlaps a dosing schedule of a UGT inhibitor schedule.
23 . A method of administering a pharmaceutical dosage form of claim 1 to a subject in need thereof with a CYP3A4 inducers, or on a dosing schedule that overlaps a dosing schedule of a CYP3A4 inducer schedule.
24 . The method of claim 14 , wherein the subject in has one or more disorders selected from the group of Tourette syndrome, transient tic disorder, chronic tic disorder, childhood onset fluency disorder (stuttering), Restless Legs Syndrome, refractory Restless Leg Syndrome, Restless Legs Syndrome with Augmentation, Augmentation associated with Restless Legs Syndrome, or a speech disorder selected from one or more of expressive language disorder, mixed receptive-expressive language disorder, phonological disorder and communication disorder not-otherwise-specified.
25 . The method of claim 24 , wherein the subject has Tourette syndrome.
26 . The method of claim 24 , wherein the subject has one or more disorders selected from the group of childhood onset fluency disorder (stuttering).
27 . The method of claim 24 , wherein the subject has one or more disorders selected from the group of Restless Legs Syndrome, refractory Restless Leg Syndrome, Restless Legs Syndrome with Augmentation, or Augmentation associated with Restless Legs Syndrome.
28 . The method of claim 14 , comprising administering the pharmaceutical dosage form to achieve a total daily dose of less than 2 mg/kg, 1.5 mg/kg or less, 1 mg/kg or less, or 0.5 mg/kg or less.
29 . The method of claim 14 , comprising administering the pharmaceutical dosage form to achieve a total daily dose of at least 25% less, or at least 50% less, or at least 75% less than a total daily dose needed for an oral dosage form which provides for absorption of ecopipam in the GI tract.
30 . A method of treating of treating a disorder comprising administering to a subject in need thereof the pharmaceutical dosage form of claim 1 , wherein the subject has one or more disorders selected from the group of Tourette syndrome, transient tic disorder, chronic tic disorder, childhood onset fluency disorder (stuttering), Restless Legs Syndrome, refractory Restless Leg Syndrome, Restless Legs Syndrome with Augmentation, Augmentation associated with Restless Legs Syndrome.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 16, 2025
From: WANASKI, STEPHEN P.; SCHMITH, VIRGINIA D.; WHITE, JAY A.; CUNNIFF, TIMOTHY M.
To: EMALEX BIOSCIENCES, INC.
Reel/Frame 073228/0775 →
Continuity (3)
Continuation
PCTUS2025020111
· Mar 14, 2025
Provisional Application
63565834
· Mar 15, 2024
References Cited (363)
US 4477378A
· Gold et al.
· 1984
[cited by applicant]
US 4973586A
· Berger et al.
· 1990
[cited by applicant]
US 5302716A
· Berger et al.
· 1994
[cited by applicant]
US 5607967A
· Friedman et al.
· 1997
[cited by applicant]
US 6132724A
· Blum
· 2000
[cited by applicant]
US 7202233B2
· Penkler
· 2007
[cited by applicant]
US 9949983B2
· Chipkin
· 2018
[cited by applicant]
US 20030109532A1
· Sonesson et al.
· 2003
[cited by applicant]
US 20040122065A1
· Lerner et al.
· 2004
[cited by applicant]
US 20070202057A1
· Fankhauser et al.
· 2007
[cited by applicant]
US 20090156581A1
· Dillon et al.
· 2009
[cited by applicant]
US 20100168085A1
· Eisenbach-Schwartz et al.
· 2010
[cited by applicant]
US 20100255086A1
· Ovil
· 2010
[cited by applicant]
US 20110206782A1
· Zhang
· 2011
[cited by applicant]
US 20110262442A1
· Hamilton et al.
· 2011
[cited by applicant]
US 20180110738A1
· Zerbe et al.
· 2018
[cited by applicant]
US 20210275540A1
· Chipkin et al.
· 2021
[cited by applicant]
US 20240189331A1
· Bilal et al.
· 2024
[cited by applicant]
CA 2465869A1
· 2003
[cited by applicant]
EP 0351733B1
· 1995
[cited by applicant]
EP 2872145B1
· 2022
[cited by applicant]
JP 10509139A
· 1998
[cited by applicant]
WO 9301702A1
· 1993
[cited by applicant]
WO 9313073A1
· 1993
[cited by applicant]
WO 9525102A1
· 1995
[cited by applicant]
WO 9613257A1
· 1996
[cited by applicant]
WO 9921540A2
· 1999
[cited by applicant]
WO 2002100350A2
· 2002
[cited by applicant]
WO 0339468A2
· 2003
[cited by applicant]
WO 2011057199A1
· 2011
[cited by applicant]
WO 2012039660A1
· 2012
[cited by applicant]
WO WO2012033874A1
· 2012
[cited by applicant]
WO WO2014012063A1
· 2014
[cited by applicant]
WO WO2024074986A1
· 2024
[cited by applicant]
WO WO2024102381A1
· 2024
[cited by applicant]
Salehi, “Improving Dissolution Behavior and Oral Absorption of Drugs with pH-Dependent Solubility Using pH Modifiers: A Physiologically Realistic Mass Transport Analysis”, Mol. Pharmaceutics 2021, 18, 3326-3341.
[cited by examiner]
Aldawsari et al., “Enhanced pharmacokinetic performance of dapoxetine hydrochloride via the formulation of instantly-dissolving buccal films with acidic pH modifier and hydrophilic cyclodextrin: Factorial analysis, in v…
[cited by applicant]
Clinical Trails—NCT01408394, “Safety and Tolerability Comparison of Immediate and Controlled Release Formulations of Ecopipam,” 10 pages (2024).
[cited by applicant]
Clinical Trials—NCT04902105, “Drug-Drug Interaction Study to Evaluate the Effect of Inhibition of UGTs on the PK of Ecopipam and Its Active Metabolite,” 21 pages (2021).
[cited by applicant]
Clinical Trials—NCT05841160, “Thorough QT/QTc Study to Evaluate the Effects of Ecopipam (EBS-101) on Cardiac Repolarization,” 27 pages, (2023).
[cited by applicant]
Gilbert et al., “A D1 Receptor Antagonist, Ecopipam, for Treatment of Tics in Tourette Syndrome,” Clinical Neuropharmacology, 37(1):26-30 (2014).
[cited by applicant]
Gilbert et al., “Ecopipam for Tourette Syndrome: A Randomized Trial,” Pediatrics, 151(2):10 pages (2023).
[cited by applicant]
He et al., “Microenvironmental pH Modification in Buccal/Sublingual Dosage Forms for Systemic Drug Delivery,” Pharmaceutics 15:637, 18 pages (2023).
[cited by applicant]
Maguire et al., “Ecopipam as a pharmacologic treatment of stuttering,” Annals of Clinical Psychiatry, 31(3):164-168 (2019).
[cited by applicant]
Ondo et al., “Exploratory cross-over, trial of augmented RLS with the dopamine receptor 1/5 antagonist ecopipam D1/D5 antagonist ecopipam for augmented RLS,” International Journal of Neuroscience, 132(8):778-782 (2022).
[cited by applicant]
Qiang et al., “Discovery of new SCH 39166 analogs as potent and selective dopamine D1 receptor antagonists,” Bioorganic & Medicinal Chemistry Letters, 20:836-840 (2010).
[cited by applicant]
Sabra et al., “Buccal Absorption of Biopharmaceutics Classification System III Drugs: Formulation Approaches and Mechanistic Insights,” Pharmaceutics, 16:1563, 15 pages (2024).
[cited by applicant]
Schmith et al., “The Effect of UGT Inhibition on the Pharm Aco Kin-Etics of Ecopipam and Its Metabolites,” Dialog, Supplement 1, 113, S71 (2023).
[cited by applicant]
Study Details—NCT06194864, “Drug Interaction Study”, 20 pages (2024).
[cited by applicant]
Tephly et al., “Studies on the Glucuronidation of Dopamine D-1 Receptor Antagonists, SCH 39166 and SCH 23390, by Human Liver Microsomes,” Drug Metabolism and Disposition, 22(5):713-718 (1994).
[cited by applicant]
Wanaski et al., “The Effect of Ecopipam and its Metabolites on Cardiac Repolarization, QTcF (P10-5.014)”, Neurology, 104, 3 pages (2025).
[cited by applicant]
International Search Report and Written Opinion from International Application No. PCT/US2025/020111 dated Jun. 26, 2025.
[cited by applicant]
Smith, “American Society for Clinical Pharmacology and Therapeutics”, Clinical Pharmacology and Therapeutics, 113(S1), pp. 1-96 (2023).
[cited by applicant]
“Acute Oral and Intraperitoneal Toxicity Studies of SCH 39166 (HCI) in Mice”, Report No. P-5326, Study No. 88089, 88090 (Oct. 24, 1988).
[cited by applicant]
“Acute Oral and Intraperitoneal Toxicity Studies of SCH 39166 (HCI) in Rats”, Report No. P-5325, Study No. 88087, 88088 (Oct. 24, 1988).
[cited by applicant]
“Examination Report corresponding to European Application No. 16837850.3 dated Apr. 6, 2021”.
[cited by applicant]
“Summons to attend oral proceedings corresponding to European Application No. 16837850.3 dated Sep. 2, 2022”.
[cited by applicant]
Allen et al. “A randomized, double-blind, 6-week, dose-ranging study of pregabalin in patients with restless legs syndrome” Sleep Medicine, 11(6):512-519 (2010) (Abstract only).
[cited by applicant]
Allen et al. “Augmentation of the restless legs syndrome with carbidopa/levodopa” Sleep, 19(3):205-213 (1996) (Abstract only).
[cited by applicant]
Allen et al. “Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria—history, rationale, description, and significance” Slee…
[cited by applicant]
Allouche et al. “Opioid receptor desensitization: mechanisms and its link to tolerance” Frontiers in Pharmacology 5(280):1-20 (2014).
[cited by applicant]
Anonymous: “Clinical Trials Archive—History of Changes for Study: NCT0124463333”, May 8, 2012 (May 8, 2012).
[cited by applicant]
Anonymous: “Ecopipam tablets to Study Tourette's syndrome in children and adolescents (DIAMOND)”, Apr. 21, 2022, pp. 1-21.
[cited by applicant]
Arnt et al., The citalopram/5-HTP-induced head shake syndrome is correlated to 5-HT2 receptor affinity and also influenced by other transmitters., Acta Pharmacol Toxicol (Copenh), 55(5):363-372 (1984).
[cited by applicant]
Ashurst, John et al., Developmental and Persistent Developmental Stuttering: An Overview For Primary Care Physicians, Journal of American Osteopathic Associations, 111, 576-580, 2011.
[cited by applicant]
Astrup et al., “Randomized Controlled Trials of the D1/D5 Antagonist Ecopipam for Weight Loss in Obese Subjects,” Obesity, 15(7):1717-1731 (2007).
[cited by applicant]
Baier et al. “Circadian variation in restless legs syndrome” Sleep Medicine, 8(6):645-650 (2007) (Abstract only).
[cited by applicant]
Barriere et al. “The restless legs syndrome” Progress in Neurobiology, 77(3):139-165 (2005) (Abstract only).
[cited by applicant]
Bayard et al. “Decision-making, Reward-Seeking Behaviors and Dopamine Agonist Therapy in Restless Legs Syndrome” Sleep, 36(10):1501-1507 (2013).
[cited by applicant]
Beaulieu and Gainetdinov, The Physiology, Signaling, and Pharmacology of Dopamine Receptors, Pharmacol Rev 63(1):182-217 (2011).
[cited by applicant]
Bedard et al., The ‘wet dog shake’ behaviour in the rat and 5-hydroxytryptamine, Br J Pharmacol 59(3): 450P-451P (1977).
[cited by applicant]
Bekhit, M.H. “Opioid-induced hyperalgesia and tolerance” American Journal of Therapeutics, 17(5):498-510 (2010) (Abstract only).
[cited by applicant]
Berge, et al., Pharmaceutical Salts, Journal of Pharmaceutical Sciences 66(1): 1-19 (1977).
[cited by applicant]
Blomgren, Michael, Behavioral Treatments For Children and Adults Who Stutter: a Review, Psychol. Res. Behav. Management, 6:9-19, 2013.
[cited by applicant]
Bonnier et al., Ketanserin treatment of Tourette's Syndrome in children, American Journal of Psychiatry 156(7):1122a-1123 (1999).
[cited by applicant]
Borowski et al., Blood Pressure Response to Thyrotropin-Releasing Hormone in Euthyroid Subjects, J Clin Endocrinol Metab 58(1):197-200 (1984).
[cited by applicant]
Bothe, AK et al., Stuttering Treatment Research 1970-2005. I: Systematic Review Incorporating Trial Quality Assessment of Behavioral, Cognitive, and Related Approaches, American Journal of Speech-Language Pathology, 15:…
[cited by applicant]
Boyd, A et al., Pharmacological Agents for Developmental Stuttering in Children and Adolescents: A Systemic Review, J. Clin. Psychopharmacol., 31(6):740-744, 2011.
[cited by applicant]
Braun, et al. “Selective D-1 dopamine receptor agonist effects in hyperkinetic extrapyramidal disorders,” Journal of Neurology, Neurosurgery and Psychiatry (1989) vol. 52, pp. 631-635.
[cited by applicant]
Breese et al. “Peripheral inflammation selectively increases TRPV1 function in 114-positive sensory neurons from adult mouse” Pain, 115(1-2):37-49 (2005) (Abstract only).
[cited by applicant]
Brett et al., “The Genetic Susceptibility to Gilles de la Tourette Syndrome in a Large Multiple Affected British Kindred: Linkage Analysis Excludes a Role for the Genes Coding for Dopamine D1, D2, D3, D4, D5 Receptors, …
[cited by applicant]
Brewer et al. “Dopamine D3 receptor dysfunction prevents anti-nociceptive effects of morphine in the spinal cord” Frontiers in Neural Circuits, 8:62-01-62-10 (2014).
[cited by applicant]
Bubenikova-Valesova et al. “The effect of a full agonist/antagonist of the D1 receptor on locomotor activity, sensorimotor gating and cognitive function in dizocilpine-treated rats” International Journal of Neuropsychop…
[cited by applicant]
Buchel et al., What Causes Stuttering?, PLoS Biology, 2(2):159-163 (2004).
[cited by applicant]
Castellano et al., Post-training dopamine receptor agonists and antagonists affect memory storage in mice irrespective of their selectivity for D1 or D2 receptors. Behav Neural Biol 56(3):283-91 (1991).
[cited by applicant]
Cavanna et al., The Behavioral Spectrum of Gilles de la Tourette Syndrome, Journal of Neuropsychiatry and Clinical 'Jeurosciences 13-23 (2009).
[cited by applicant]
Chahine et al. “Restless legs syndrome: a review” CNS Spectrums, 11(7):511-520 (2006) (Abstract only).
[cited by applicant]
Chipkin et al., Pharmacological Profile of SCH39166: A Dopamine D1 Selective Benzonaphthazepine With Potential Antipsychotic Activity, Journal of Pharmacology and Experimental Therapeutics 247(3) : 1093-1102 (1988).
[cited by applicant]
Cianchetti, C. et al. “Pergolide improvement in neuroleptic-resistant Tourette cases: various mechanisms causing tics,” Neurol. Sci. (2005) vol. 26, No. 2, pp. 137-139.
[cited by applicant]
Civelli et al., Molecular Diversity of the Dopamine Receptors, Annual Review of Pharmacology and Toxicology, 32:281-307 (1993).
[cited by applicant]
Clemens et al. “Conversion of the Modulatory Actions of Dopamine on Spinal Reflexes from Depression to Facilitation in D3 Receptor Knock-Out Mice” The Journal of Neuroscience, 24(50):11337-11345 (2004).
[cited by applicant]
Clemens et al. “Restless legs syndrome: revisiting the dopamine hypothesis from the spinal cord perspective” Neurology, 67(1):125-130 (2006).
[cited by applicant]
Clemens et at. “Opposing modulatory effects of D1- and D2-like receptor activation on a spinal central pattern generator” Journal of Neurophysiology, 107(8):2250-2259 (2012).
[cited by applicant]
ClinicalTrials.gov “Ecopipam Treatment of Tourette's Syndrome in Subjects 7-17 Years” https://clinicaltrials.gov/ct2/show/study/NCT02102698#wrapper (9 pages) (2014).
[cited by applicant]
Communication pursuant to Article 94(3) EPC in European Application No. 13815988.4, dated Apr. 19, 2017, in 4 pages.
[cited by applicant]
Communication pursuant to Article 94(3) EPC in European Application No. 13815988.4, dated Jun. 25, 2018.
[cited by applicant]
Connor et al. “Postmortem and imaging based analyses reveal CNS decreased myelination in restless legs syndrome” Sleep Medicine, 12(6):614-619 (2011).
[cited by applicant]
Corne et al., A Method for Assessing the Effects of Drugs on the Central Actions of 5-Hydroxytryptamine, Brit J Pharmacol 20: 106-120 (1963).
[cited by applicant]
Costa, Daniel et al., Stuttering: an Update for Physicians, Canadian Medical Association Journal, 162:1849-1855, 2000.
[cited by applicant]
Cote et al. “In vitro and in vivo characterization of the agonist-dependent D3 dopamine receptor tolerance property” Neuropharmacology, 79:359-367 (2014) (Abstract only).
[cited by applicant]
Crosley, Decreased serotoninergic activity in Tourette syndrome, Ann. Neurol., 5(6):596-7 (Jun. 1979).
[cited by applicant]
Cruz-Trujillo et al. “D3 dopamine receptors interact with dopamine D1 but not D4 receptors in the GABAergic terminals of the SNr of the rat” Neuropharmacology, 67:370-378 (2013) (Abstract only).
[cited by applicant]
Darmopil et al. “Genetic inactivation of dopamine D1 but not D2 receptors inhibits L-DOPA-induced dyskinesia and histone activation” Biological Psychiatry, 66(6):603-613 (2009) (Abstract only).
[cited by applicant]
Dauvilliers et al. “Restless legs syndrome: update on pathogenesis” Current Opinion in Pulmonary Medicine, 19(6):594-600 (2013) (Abstract only).
[cited by applicant]
Davies S. “Rotigotine for restless legs syndrome” Drugs Today (Barc), 45(9):663-668 (2009) (Abstract only).
[cited by applicant]
De Beaurepaire et al., “An Open Trial of the D1 Antagonist SCH 39166 in Six Cases of Acute Psychotic States,” Psychopharmacology, 121:323-327 (1995).
[cited by applicant]
Deandrade et al. “Motor restlessness, sleep disturbances, thermal sensory alterations and elevated serum iron levels in Btbd9 mutant mice” Human Molecular Genetics 21(18):3984-3992 (2012).
[cited by applicant]
Den Boer et al., “Differential Effects of the D1-DA Receptor Antagonist SCH39166 on Positive and Negative Symptoms of Schizophrenia,” Psychopharmacology, 121:317-322 (1995).
[cited by applicant]
Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR], Fourth Edition, American Psychiatric Association (2000). Table of Contents.
[cited by applicant]
Dinkins et al. Long-term treatment with dopamine L3 receptor agonists induces a behavioral switch that can be rescued by blocking the dopamine D1, Sleep Medicine 40:47-52 (2017).
[cited by applicant]
Djouhri et al. “Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors” The Journal of Neuroscience, 26(4):1281-1292 (2006).
[cited by applicant]
Dougherty et al. “Properties of mouse spinal lamina I GABAergic interneurons” Journal of Neurophysiology, 94(5):3221-3227 (2005).
[cited by applicant]
Drago et al. “Altered striatal function in a mutant mouse lacking D1A dopamine receptors” Proc Nat[ Acad Sci USA, 91(26):12564-12568 (1994).
[cited by applicant]
Duffy et al., In vivo autoradiography of [3H]SCH 39166 in rat brain: selective displacement by D1/D5 antagonists, Journal of Chemical Neuroanatomy 19:41-46 (2000).
[cited by applicant]
Dunlap, “TSA: Psyadon to collaborate on drug trial”, https://xmssouiitsa.ors:/2011/05/12/lsa-psvadon-to-coliaboiBte-on-dmg-tfial/. May 12, 2011, Missouri.
[cited by applicant]
Dursun, S.M. et al., “Similarities in the pharmacology of spontaneous and DOI-induced head-shakes suggest 5HT2A receptors are active under physiological conditions,” Psychopharmacology (1996) vol. 128, No. 2, pp. 198-20…
[cited by applicant]
Dziewczapolski et al. “Opposite roles of D1 and D5 dopamine receptors in locomotion revealed by selective antisense oligonucleotides” Neuroreport, 9(1):1-5 (1998) (Abstract only).
[cited by applicant]
Earley et al. “Altered Brain iron homeostasis and dopaminergic function in Restless Legs Syndrome (Willis-Ekbom Disease)” Sleep Medicine, 15(11):1288-1301 (2014) (Abstract only).
[cited by applicant]
Earley et al. “Increased synaptic dopamine in the putamen in restless legs syndrome” Sleep, 36(1):51-57 (2013).
[cited by applicant]
Earley, C.J. “Latest guidelines and advances for treatment of restless legs syndrome” The Journal of Clinical Psychiatry, 75(4):e08 (2014) (Abstract only).
[cited by applicant]
Ecopipam, Wikipedia, Apr. 26, 2013, Retrieved from the Internet: URL:https://en.wikipedia.org/wiki/Ecopipam, 4 Pages.
[cited by applicant]
Emilien et al., Dopamine receptors—physiological understanding to therapeutic intervention potential, Pharmacology and Therapeutics 84:133-156 (1999).
[cited by applicant]
England et al. “L-Dopa improves Restless Legs Syndrome and periodic limb movements in sleep but not Attention-Deficit-Hyperactivity Disorder in a double-blind trial in children” Sleep Medicine, 12(5):471-477 (2011).
[cited by applicant]
Erman, M.K. “Selected sleep disorders: restless legs syndrome and periodic limb movement disorder, sleep apnea syndrome, and narcolepsy” The Psychiatric Clinics of North America, 29(4):947-967; abstract viii-ix (2006) (…
[cited by applicant]
European Patent Application No. 13815988.4, Communication Pursuant to Article 94(3) EPC, dated Jul. 11, 2019.
[cited by applicant]
European Patent Application No. 13815988.4, Intention to Grant and related communication under Rule 71(3) EPC with text intended for grant, May 19, 2021.
[cited by applicant]
European Patent Application No. 13815988.4, Summons to Attend Oral Proceedings Pursuant to Rule 115(1) EPC, Oct. 19, 2020.
[cited by applicant]
European Search Report issued in connection with European Patent Application No. 14854586.6, dated Sep. 5, 2017, 10 pages.
[cited by applicant]
Extended European Search Report corresponding to European Application No. 16837850.3 dated May 22, 2019.
[cited by applicant]
Extended European Search Report for Application No. 13815988.4, dated Nov. 3, 2015.
[cited by applicant]
Felling and Singer, Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation, Journal of Neuroscience 31(35):12387-12395 (2011).
[cited by applicant]
Fenu et al., Differential involvement of dopamine D1 receptors in morphine- and lithium-conditioned saccharin avoidance Physiology & Behavior 96: 73-77 (2009).
[cited by applicant]
Ferini-Strambi (Restless legs syndrome augmentation and pramipexole treatment, Sleep Medicine, vol. 3, Supplement, 2002, pp. S23-S25, ISSN 1389-9457).
[cited by applicant]
Fiorentini et al. “Reciprocal regulation of dopamine D1 and D3 receptor function and trafficking by heterodimerization” Molecular Pharmacology, 74(1):59-69 (2008).
[cited by applicant]
First Office Action issued in Chinese Patent Application No. 2013800369039, dated Jan. 6, 2016.
[cited by applicant]
Fourth Office Action issued in Chinese Patent Application No. 2013800369039, dated May 9, 2018.
[cited by applicant]
Garcia-Borreguero et al. “Algorithms for the diagnosis and treatment of restless legs syndrome in primary care” BMC Neurology, 11:28 (2011).
[cited by applicant]
Garcia-Borreguero et al. “Augmentation as a treatment complication of restless legs syndrome: concept and management” Movement Disorders, 22(S18):S476-S484 (2007) (Abstract only).
[cited by applicant]
Garcia-Borreguero et al. “Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine—International Restless Legs Syndrome Study Group consensus confer…
[cited by applicant]
Garcia-Borreguero et al. “Dopaminergic augmentation of restless legs syndrome” Sleep Medicine Reviews, 14(5):339-346 (2010) (Abstract only).
[cited by applicant]
Garcia-Borreguero et al. “Epidemiology of restless legs syndrome: the current status” Sleep Medicine Reviews, 10(3):153-167 (2006) (Abstract only).
[cited by applicant]
Garcia-Borreguero et al. “Systematic evaluation of augmentation during treatment with ropinirole in restless legs syndrome (Willis-Ekbom disease): results from a prospective, multicenter study over 66 weeks” Movement Di…
[cited by applicant]
Garcia-Borreguero et al. “The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Sy…
[cited by applicant]
Garcia-Borreguero et al. “Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study” Neurology, 74(23):1897-1904 (2010).
[cited by applicant]
Garcia-Borreguero et al. “Validation of the Augmentation Severity Rating Scale (ASRS): a multicentric, prospective study with levodopa on restless legs syndrome” Sleep Medicine, 8(5):455-463 (2007) (Abstract only).
[cited by applicant]
Gelernter et al., “Exclusion of close Linkage of Tourette's Syndrome to D1 Dopamine Receptor,” Am. J. Psychiatry, 150(3):449-453 (1993).
[cited by applicant]
Gil-Mast et al. “An amino acid residue in the second extracellular loop determines the agonist-dependent tolerance property of the human D3 dopamine receptor” ACS Chemical Neuroscience, 4(6):940-951 (2013).
[cited by applicant]
Gilbert et al. “Tourette's syndrome improvement with pergolide in a randomized, double-blind crossover trial,” Neurology (2000) vol. 54, No. 6, pp. 1310-1315.
[cited by applicant]
Gilbert et al., “Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in children: A randomized, placebo-controlled crossover study”, Internationlal Perkinson and Movement Disorder Society, vol. 33, No…
[cited by applicant]
Gilbert, D.L. et al. “Tic reduction with pergolide in a randomized controlled trial in children,” Neurology (2003) vol. 60, No. 4, pp. 606-611.
[cited by applicant]
Gobira et al., Animal models for predicting the efficacy and side effects of antipsychotic drugs, Revista Brasileira de Psiquiatria 35: S132-S139 (2013).
[cited by applicant]
Godar et al., Animal models of tic disorders: A translational perspective, J. Neurosci. Methods, 238:54-69 (Dec. 2014).
[cited by applicant]
Granado et al. “D1 but not D4 dopamine receptors are critical for MDMA-induced neurotoxicity in mice” Neurotoxicit Research, 25(1):100-109 (2014).
[cited by applicant]
Grant et al., “A Single-Blind Study of ‘As-Needed’ Ecopipam for Gambling Disorder,” Annals of Clinical Psychiatry, 26(3): 1 79-186 (2014).
[cited by applicant]
Griesemer, D.A. “Pergolide in the management of Tourette Syndrome,” Journal of Child Neurology (1997) vol. 12, No. 6, pp. 402-403.
[cited by applicant]
Guitart et al. “Functional Selectivity of Allosteric Interactions within G Protein-Coupled Receptor Oligomers: The Dopamine D1-D3 Receptor Heterotetramer” Molecular Pharmacology, 86(4):417-429 (2014).
[cited by applicant]
Haile et al., The dopamine D1 receptor agonist SKF-82958 serves as a discriminative stimulus in the rat, European Journal of Pharmacology 388: 125-131 (2000).
[cited by applicant]
Hall et al. “Changes in mood, depression and suicidal ideation after commencing pregabalin for neuropathic pain” Australian Family Physician, 43(10):705-708 (2014).
[cited by applicant]
Han Dley et al., Serotonin and Tourette's Syndrome: Movements Such as Head-Shakes and Wet-Dog Shakes May Model Human Tics, pp. 235-253 In: Bradley et al. (eds), Serotonin, CNS Receptors and Brain Function, Proceedings o…
[cited by applicant]
Han et al. “Dopaminergic modulation of spinal neuronal excitability” The Journal of Neuroscience, 27(48):13192-1320 (2007).
[cited by applicant]
Han et al. “Modulation of AMPA currents by D(1)-like but not D(2)-like receptors in spinal motoneurons” Neuroscience, 158(4):1699-1707 (2009).
[cited by applicant]
Haney et al., Controversies in Translational Research: Drug self-administration, Psychopharmacology, 1 99(3):403-41 9 (2008).
[cited by applicant]
Haugbol et al., Cerebral 5-HT2A receptor binding is increased in patients with Tourette's syndrome, Int. J. Neuropsychopharmacol., 10(2):245-52 (Apr. 2007).
[cited by applicant]
Hayslett et al., Effects of donepezil on DOI-induced head twitch response in mice: implications for Tourette syndrome, Pharmacol. Biochem. Behav., 76(3-4):409-15 (Dec. 2003).
[cited by applicant]
Hayslett et al., Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome, Pharmacol. Biochem. Behav., 81 (4):879-86 (Aug. 2005).
[cited by applicant]
Himle et al., Establishing the feasibility of direct observation in the assessment of tics in children with chronic tic disorders, Journal of Applied Behavior Analysis 39: 429-440 (2006).
[cited by applicant]
Hogl et al. “Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study” Journal of Neurology, 257(2):230-237 (2010).
[cited by applicant]
Hollis et al., Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis, Health Technolo…
[cited by applicant]
Huang et al. “Smad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodeling” Hypertension, 55(5):1165-1171 (2010).
[cited by applicant]
Hubble, J.P. “Pre-clinical studies of pramipexole: clinical relevance” European Journal of Neurology, 7(S1 ):15-20 (2000) (Abstract only).
[cited by applicant]
Ingham, Roger et al., Towards a Functional Neural Systems Model of Developmental Stuttering, J. Fluency Disord., 28(4):297-317, 2003.
[cited by applicant]
International Application No. PCT/US23/36986, International Preliminary Report on Patentability, mailed May 22, 2025.
[cited by applicant]
International Application No. PCT/US23/36986, International Search Report and Written Opinion, mailed Feb. 21, 2024.
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/U52014/061080, dated Apr. 19, 2016.
[cited by applicant]
International Search Report and the Written Opinion of the International Searching Authority corresponding to International Patent Application No. PCT/US2016/047591 (14 pages) (mailed Nov. 30, 2016).
[cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2014/061080, dated Dec. 24, 2014.
[cited by applicant]
International Search Report and Written Opinion of the International Searching Authority for PCT/US2013/050337, Nov. 14, 2013.
[cited by applicant]
Iuga et al. “ROS initiated oxidation of dopamine under oxidative stress conditions in aqueous and lipidic environments” The Journal of Physical Chemistry B, 115(42):12234-12246 (2011).
[cited by applicant]
Jankovic et al., “Tourette's Syndrome and the Law,” J. Neuropsychiatry Clin. Neurosci, 18(1):86-95 (2006).
[cited by applicant]
Jankovic J., Tourette's Syndrome, The New England Journal of Medicine, 345(16): 1184-1192 (2001).
[cited by applicant]
Johnson et al. “The dopamine D3 receptor knockout mouse mimics aging-related changes in autonomic function and cardiac fibrosis” PLoS One, 8(8):e74116 (2013).
[cited by applicant]
Karlsson et al., Evaluation of SCH 39166 as PET ligand for central D1 dopamine receptor binding and occupancy in man, Psychopharmacology (Berl) 121(3):300-308 (1995).
[cited by applicant]
Karlsson et al., Lack of apparent antipsychotic effect of the D1-dopamine receptor antagonist SCH39166 in acutely ill schizophrenic patients, Psychopharmacology (Berl) 121(3): 309-316 (1995).
[cited by applicant]
Karson et al., Eye-blink rate in Tourette's syndrome, J Nerv Ment Dis 173(9): 566-569 (1985).
[cited by applicant]
Keeler et al. “Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse” Experimental Neurology, 238(2):273-283 (2012) (Abstract only).
[cited by applicant]
Keeler et al. “Opposing aging-related shift of excitatory dopamine D1 and inhibitory D3 receptor protein expression in striatum and spinal cord” Journal of Neurophysiology, 115:363-369 (2016).
[cited by applicant]
Kenney et al., Tourette's Syndrome, American Family Physician 77(5):651-658 (2008).
[cited by applicant]
Khasnavis et al., A double-blind, placebo-controlled, crossover trial of the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease, Mol. Genet. Metab., 118:160-6 (2016).
[cited by applicant]
Kraft, SJ et al., Genetic Bases of Stuttering: The State of the Art, 2011, Folia Phoniatr Logop, 64(1):34-47, 2012.
[cited by applicant]
Kurlan, “Tourette's Syndrome” The New England Journal of Medicine 363 2332-2338, 2010.
[cited by applicant]
Kustermann et al. “Depression and attempted suicide under pregabalin therapy” Annals of General Psychiatry, 13(1):37 (2014).
[cited by applicant]
Kuzhikandathil et al. “Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells” The Journal of Neuroscience, 19(5):1698-1707 (1999).
[cited by applicant]
Kuzhikandathil et al. “Identification and characterization of novel properties of the human D3 dopamine receptor” Molecular and Cellular Neurosciences, 26(1):144-155 (2004) (Abstract only).
[cited by applicant]
Leckman et al., “Tic Disorders: When Habit Forming Neural Systems Form Habits of Their Own?” Chinese Medical Journal (Taipei), 64:669-692 (2001).
[cited by applicant]
Leckman et al., Course of Tic Severity in Tourette Syndrome: The First Two Decades, Pediatrics 102:14-19 (1998).
[cited by applicant]
Lipinski, J.F. et al. “Dopamine agonist treatment of Tourette disorder in children: Results of an open-label trial of pergolide,” Movement Disorders (1997) vol. 12, No. 3, pp. 402-407.
[cited by applicant]
Luo et al. “The long-term effects of the dopamine agonist pramipexole in a proposed restless legs syndrome animal model” Sleep Medicine, 12(1):41-46 (2010) (Abstract only).
[cited by applicant]
Machacek et al. “Serotonin 5-HT(2) receptor activation induces a long-lasting amplification of spinal reflex actions in the rat” The Journal of Physiology, 537(Pt 1):201-207 (2001).
[cited by applicant]
Mackie et al. “Long-Term Treatment of Restless Legs Syndrome (RLS): An Approach to Management of Worsening Symptoms, Loss of Efficacy, and Augmentation” CNS Drugs, 29(5):351-357 (2015).
[cited by applicant]
Maggio et al. “Heterodimerization of dopamine receptors: new insights into functional and therapeutic significance” Parkinsonism and Related Disorders, 15(Suppl 4):S2-S7 (2009) (Abstract only).
[cited by applicant]
Maguire, G. et al., Exploratory Randomized Clinical Study of Pagoclone in Persistent Developmental Stuttering: The Examining Pagoclone for Persistent Developmental Stuttering Study., J. Clin. Psychopharmacol. 30:48-56, …
[cited by applicant]
Maguire, Gerald et al., Alleviating Stuttering with Pharmacological Interventions, Expert Opinion on Pharmacotherapy, vol. 5, No. 7, 1565-1571, Jan. 2004.
[cited by applicant]
Maguire, Gerald et al., Risperidone for the Treatment of Stuttering, Journal of Clinical Psychopharmacology, vol. 20, No. 4, 479-482, Aug. 2000.
[cited by applicant]
Malik et al. “The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia” Pharmacology, Biochemistry, and Behavior, 78(4):805-810 (2004) (Abstract only).
[cited by applicant]
Manconi et al. “First night efficacy of pramipexole in restless legs syndrome and periodic leg movements” Sleep Medicine, 8(5):491-497 (2007) (Abstract only).
[cited by applicant]
Manconi et al. “Preferential D2 or preferential D3 dopamine agonists in restless legs syndrome” Neurology, 77(2):110-117 (2011).
[cited by applicant]
Marek, Behavioral evidence for mu-opioid and 5-HT2A receptor interactions, Eur. J. Pharmacol., 474(1):77-83 (Aug. 2003).
[cited by applicant]
Markham, Pergolide: A Review of its Pharmacology and Therapeutic Use in Parkinson's Disease, 3NS Drugs 7(4):328-340 (1997).
[cited by applicant]
Massad et al. “Vitamin B-sensitized photo-oxidation of dopamine” Photochemistry and Photobiology, 84(5):1201-1208 (2008) (Abstract only).
[cited by applicant]
McCreary, et al., The thyrotrophin-releasing hormone analogue MK771 induces tic-like behaviors: the effects of dopamine Di and D2 receptor antagonists, European Journal of Pharmacology, (1999) vol. 369, pp. 1-9.
[cited by applicant]
Mcquade et al., In vivo binding of SCH 39166: a D-1 selective antagonist, J Pharmacol Exp Ther 257(1) 42-49 (1991).
[cited by applicant]
Mcquade,, Robert et al., [3H]SCH 39166, A New D1-Selective Radioligand: In Vitro and In Vivo Binding Analyses, Journal of Neurochemistry, 57(6), 2001-2010, 1991.
[cited by applicant]
Meneely et al. Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome, Frontiers in Behavioral Neuroscience vol. 12 (2018) 14 pages.
[cited by applicant]
Missale et al. “The neurobiology of dopamine receptors: evolution from the dual concept to heterodimer complexes” Journal of Receptor and Signal Transduction Research, 30(5):347-354 (2010) (Abstract only).
[cited by applicant]
Montplaisir et al. “Restless legs syndrome improved by pramipexole: a double-blind randomized trial” Neurology, 52(5):938-943 (1999) (Abstract only).
[cited by applicant]
Mozos-Ansorena et al., “Stuttering Treated with Olanzapine: A Case Report,” Actas Esp Psiquiatr, 40(4):231-233 (2012).
[cited by applicant]
Müller N., Tourette's syndrome: clinical features, pathophysiology, and therapeutic approaches, Dialogues Clin Neurosci. 9(2):161-71 (2007).
[cited by applicant]
Nann-Vernotica et al., “Repeated Administration of the D1/5 Antagonist Ecopipan Fails to Attenuate the Subjective Effects of Cocaine,” Psychopharmacology, 155:338-347 (2001).
[cited by applicant]
Newbury, D.F. et al., Genetic Advances in the Study of Speech and Language Disorders, Neuron, 68:309-320, 2010.
[cited by applicant]
Notice of Final Rejection for Japanese Application No. 2015-521856, dated Nov. 16, 2016.
[cited by applicant]
Notice of Final Rejection for Korean Application No. 10-2015-7001403, dated Jun. 28, 2016.
[cited by applicant]
Notice of Preliminary Rejection for Korean Application No. 10-2015-7001403, dated Oct. 6, 2016.
[cited by applicant]
Notice of Reasons for Rejection for Japanese Application No. 201 5-52 1856, dated Nov. 30, 2015.
[cited by applicant]
Notice of Reasons for Rejection for Japanese Application No. 201 6-524108, dated Jun. 27, 2018.
[cited by applicant]
Odin et al. “Restless legs syndrome” European Journal of Neurology, 9(S3):59-67 (2002) (Abstract only).
[cited by applicant]
Oertel et al. “Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study” Lancet Neurology, 10(8):710-720 (2011) (Abstrac…
[cited by applicant]
Oertel et al. “Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: a randomized, placebo-controlled polysomnographic study” Sleep Medicine, 11(9):848-856 (2010) (Abstract only).
[cited by applicant]
Office Action and Examination Search Report in Canadian Application No. 2,879,020, dated Feb. 18, 2016, in 3 pages.
[cited by applicant]
Office Action and Examination Search Report in Canadian Application No. 2,879,020, dated Jul. 14, 2017.
[cited by applicant]
Office Action and Examination Search Report in Canadian Application No. 2,879,020, dated Mar. 26, 2019.
[cited by applicant]
Office Action and Examination Search Report in Canadian Application No. 2,879,020, dated Oct. 25, 2016.
[cited by applicant]
Office Action for Israeli Application No. 236403, dated Apr. 9, 2018.
[cited by applicant]
Office Action for Israeli Application No. 236403, dated Jul. 12, 2017.
[cited by applicant]
Oliveira De Almeida et al. The effects of long-term dopaminergic treatment on locomotor behavior in rats Sleep Science, 7(4):203-208 (2014).
[cited by applicant]
Patent Examination Report No. 1 from Australian Patent Application No. 2013289922, dated Nov. 24, 2015 in 5 pages.
[cited by applicant]
Paulus et al. (Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome. The Lancet Neurology vol. 5, Issue 10, Oct. 2006, pp. 878-886).
[cited by applicant]
Paulus et al. Dopamine and the spinal cord in restless legs syndrome: does spinal cord physiology reveal a basis for augmentation, Sleep Medicine Reviews, 10(3):185-196 (2006) (Abstract only).
[cited by applicant]
Pettersson, Ingrid et al., A Study on the Contribution of the 1-Phenyl Substituent to the Molecular Electrostatic Potentials of Some Benzazepines in Relation to Selective Dopamine D-1 Receptor Activity, J. Med. Chem., v…
[cited by applicant]
Pham et al. “Cu(II)-catalyzed oxidation of dopamine in aqueous solutions: mechanism and kinetics” Journal of Inorganic Biochemistry, 137:74-84 (2014) (Abstract only).
[cited by applicant]
Phelps, “Tourette's Disorder: Genetic Update, Neurological Correlates, and Evidence-Based Interventions,” School Psychology Quarterly, 23(2):282-289 (2008).
[cited by applicant]
Phillips et al. “Prevalence and correlates of restless legs syndrome: results from the 2005 National Sleep Foundation Poll” Chest, 129(1):76-80 (2006) (Abstract only).
[cited by applicant]
Picchietti et al. “Restless legs syndrome: prevalence and impact in children and adolescents—the Peds REST study” Pediatrics, 120(2):253-266 (2007) (Abstract only).
[cited by applicant]
Prasse, Jane et al., Stuttering: An Overview, American Family Physician, 77:1271-1276, 2008.
[cited by applicant]
Pringsheim et al., Comprehensive systematic review summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders, Neurology, 92(19):907-915 (May 2019).
[cited by applicant]
Rascol, O. “Dopamine agonists: what is the place of the newer compounds in the treatment of Parkinson's disease?” Journal of Neural Transmission Supplementum, 55:33-45 (1999) (Abstract only).
[cited by applicant]
Ravin, L., “Preformulation,” Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, Chapter 76, pp. 1409-1423.
[cited by applicant]
Raz, “Translational Attention: From Experiments in the Lab to Helping the Symptoms of Individuals with Tourette's Syndrome,” Consciousness and Cognition, (21 ):1591-1594 (2012).
[cited by applicant]
Reagan-Shaw et al., “Dose translation from animal to human studies revisited,” FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 22(3):659-661 (2008).
[cited by applicant]
Risperidone, Wikipedia, Mar. 31, 2017, Retrieved from the Internet: URL:https://en.wikipedia.org/wiki/Risperidone, 17 Pages.
[cited by applicant]
Romach et al , “Attenuation of the euphoric effects of cocaine by the dopamine D1/D5 antagonist ecopipam (SCH 39166)” Archives of General Psychiatry, 1999, 56(12) 1101-1106, Dec. 1999.
[cited by applicant]
Salas et al. “All the wrong moves: a clinical review of restless legs syndrome, periodic limb movements of sleep and wake, and periodic limb movement disorder” Clinics in Chest Medicine, 31(2):383-395 (2010) (Abstract o…
[cited by applicant]
Samir et al. “Morphine responsiveness to thermal pain stimuli is aging-associated and mediated by Dopamine D1 and D3 receptor interactions” Neuroscience, 349:87-97 (2017).
[cited by applicant]
Sanberg et al., Nicotine for the treatment of Tourette's syndrome, Pharmacol. Ther., 74(1 ):21-5 (1997).
[cited by applicant]
[cited by applicant]
[cited by applicant]
Scahill, L. et al. “Pharmacologic treatment of tic disorders,” Child Adolesc. Psychiatr. Clin. N. Am. (2000) vol. 9, No. 1, pp. 99-117.
[cited by applicant]
Schindler et al., Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), Pharmacol Biochem Behav 101(1)…
[cited by applicant]
Scholz et al. “Dopamine agonists for restless legs syndrome” The Cochrane Database of Systematic Reviews, (3):CD006009 (2011) (Abstract only).
[cited by applicant]
Scholz et al. “Levodopa for restless legs syndrome” The Cochrane Database of Systematic Reviews, (2):CD005504 (2011) (Abstract only).
[cited by applicant]
Schormair et al. “MEIS1 and BTBD9: genetic association with restless leg syndrome in end stage renal disease” Journal of Medical Genetics, 48(7):462-466 (2011).
[cited by applicant]
Schormair et al. “PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome” Nature Genetics, 40(8):946-948 (2008).
[cited by applicant]
Schrieber et al., (1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5…
[cited by applicant]
Second Office Action issued in Chinese Patent Application No. 2013800369039, dated Nov. 28, 2016, in 11 pages.
[cited by applicant]
Shah et al., (+/−)-(N-alkylamino)benzazepine analogs: novel dopamine D1 receptor antagonists, Journal of Medicinal Chemistry 38(21):4284-93 (1995).
[cited by applicant]
Shaygannejad et al., Olanzapine Versus Haloperidol: Which Can Control Stuttering Better?, Int J Prev Med. 4 (Suppl 2):S270-273, 2013.
[cited by applicant]
Shin et al., “Interpretation of Animal Dose and Human Equivalent Dose for Drug Development,” The Journel of Korean Oritental Medicine, 31(3):1-7 (2010).
[cited by applicant]
Shreckengost et al. “Bicuculline-sensitive primary afferent depolarization remains after greatly restricting synaptic transmission in the mammalian spinal cord” The Journal of Neuroscience, 30(15):5283-5288 (2010).
[cited by applicant]
Silver et al. “A 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome” Sleep Medicine, 12(5):440-444 (2011) (Abstract only).
[cited by applicant]
Singer et al., “Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome,” Ann. Neurol., 30:558-562 (1991).
[cited by applicant]
Spieler et at. “Restless legs syndrome-associated intronic common variant in Meis1 alters enhancer function in the developing telencephalon” Genome Research, 24(4):592-603 (2014).
[cited by applicant]
Staley et al., Tourette disorder: a cross-cultural review, Comprehensive Psychiatry 38(1): 6-16 (1997).
[cited by applicant]
Starr et al., Differential effects of dopamine D1 and D2 agonists and antagonists on velocity of movement, earing and grooming in the mouse. Implications for the roles of D1 and D2 receptors, Neuropharmacology 25(5): 45…
[cited by applicant]
Starr et al., Grooming in the mouse is stimulated by the dopamine D1 agonist SKF 38393 and by low doses of the D1 antagonist SCH 23390, but is inhibited by dopamine D2 agonists, D2 antagonists and high doses of SCH >339…
[cited by applicant]
Stefansson et al. “A genetic risk factor for periodic limb movements in sleep” The New England Journal of Medicine, 357(7):639-647 (2007).
[cited by applicant]
Stiasny-Kolster et al. “Low-dose pramipexole in the management of restless legs syndrome. An open label trial.” Neuropsychobiology, 50(1):65-70 (2004) (Abstract only).
[cited by applicant]
Stiasny-Kolster et at. “Effectiveness and tolerability of rotigotine transdermal patch for the treatment of restless legs syndrome in a routine clinical practice setting in Germany” Sleep Medicine, 14(6):475-481 (2013) …
[cited by applicant]
Surmeier et al. “Coordinated expression of dopamine receptors in neostriatal medium spiny neurons” The Journal of Neuroscience, 16(20):6579-6591 (1996).
[cited by applicant]
Swerdlow and Sutherland, Using animal models to develop therapeutics for Tourette Syndrome, Pharmacology and Therapeutics 108(3):281-93 (2005).
[cited by applicant]
Taylor et al., Dopamine receptor modulation of repetitive grooming actions in the rat: potential relevance for Tourette syndrome, Brain Res 1322:92-101 (2010).
[cited by applicant]
Third Office Action issued in Chinese Patent Application No. 201 3800369039, dated Aug. 21, 2017.
[cited by applicant]
Thorpe et al. “Possible sites of therapeutic action in Restless Legs Syndrome: Focus on dopamine and [alpha]2 [delta] ligands” European Neurology, 66(1):18-29 (2011).
[cited by applicant]
Tizabi et al., Nicotine attenuates DOI-induced head-twitch response in mice: implications for Tourette syndrome, Prog. Neuropsychopharmacol. Biol. Psychiatry, 25(7) : 1445-57 (Oct. 2001).
[cited by applicant]
Trenkwalder et al. “Restless legs syndrome: pathophysiology, clinical presentation and management” Nature Reviews Neurology, 6(6):337-346 (2010) (Abstract only).
[cited by applicant]
Trenkwalder et al. “The restless legs syndrome” Lancet Neurology, 4(8):465-475 (2005) (Abstract only).
[cited by applicant]
Trotti et al. “Restless legs syndrome” Handbook of Clinical Neurology, 100:661-673 (2011) (Abstract Only).
[cited by applicant]
VanHole, Nicholas. Shared Consciousness: A Social History of Tourette Syndrome and its Treatments. University of Montana. ScholarWorks at University of Montana. Theses, Dissertations, Professional Papers. 2012, 123 page…
[cited by applicant]
Wei, L. “Immunological aspect of cardiac remodeling: T lymphocyte subsets in inflammation-mediated cardiac fibrosis” Experimental and Molecular Pathology, 90(1):74-78 (2011) (Abstract only).
[cited by applicant]
Weisman et al., Systematic review: pharmacological treatment of tic disorders—efficacy of antipsychotic and alpha-2 adrenergic agonist agents, Neuroscience and Biobehavioral Reviews 37(6):1162-71 (2013).
[cited by applicant]
Westrich et al. “Development of tolerance in D3 dopamine receptor signaling is accompanied by distinct changes in receptor conformation” Biochemical Pharmacology 79:897-907 (2010).
[cited by applicant]
Winkelmann et al. “Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions” Nature Genetics, 39(8):1000-1006 (2007) (Abstract only).
[cited by applicant]
Winkelmann et al. “Opioid and dopamine antagonist drug challenges in untreated restless legs syndrome patients” Sleep Medicine, 2(1):57-61 (2001) (Abstract only).
[cited by applicant]
Winkelmann et al. “Sensory symptoms in restless legs syndrome: the enigma of pain” Sleep Medicine, 14(10):934-942 (2013) (Abstract only).
[cited by applicant]
Winkelmann et at. “Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1” PLoS Genetics, 7(7):e1002171 (2011).
[cited by applicant]
Winkelmann, J. “Genetics of restless legs syndrome” Current Neurology and Neuroscience Reports, 8(3):211-216 (2008) (Abstract only).
[cited by applicant]
Xiong et al. “Molecular genetic studies of DMT1 on 12q in French-Canadian restless legs syndrome patients and families” American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 144B(7):911-917 (2007) (Abs…
[cited by applicant]
Xu et al. “Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses” Cell, 79(4):729-742 (1994).
[cited by applicant]
Xu et al. “Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine D1 receptor mutant mice” Cell, 79(6):945-955 (1994) (Abstract only).
[cited by applicant]
Yamada et al., Acute immobilization stress reduces (+/−)DOI-induced 5-HT2A receptor-mediated head shakes in rats, Psychopharmacology (Berl), 1 19(1):9-14 (May 1995).
[cited by applicant]
Zeng et al. “D3 Dopamine Receptor Directly Interacts With D1 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells” Hypertension 47(part 2):573-579 (2006).
[cited by applicant]
Zhu et al. “Expression and distribution of all dopamine receptor subtypes (D1-D5) in the mouse lumbar spinal cord: A real-time polymerase chain reaction and non-autoradiographic in situ hybridization study” Neuroscience…
[cited by applicant]
Zhu et al. “Unaltered D1, D2, D4, and D5 dopamine receptor mRNA expression and distribution in the spinal cord of the D3 receptor knockout mouse” Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and …
[cited by applicant]
Zypadhera, European Medicines Agency, Apr. 25, 2014, XP002769139, 7 Pages.
[cited by applicant]
Atkinson et al., Efficacy, Safety, and Tolerability of Ecopipam in Tourette Syndrome With Psychiatric Comorbidities, American Psychiatric Association, Poster 4519, 1 Page (May 2023).
[cited by applicant]
Clinical Trials—NCT01065558, Study Details, “Safety and Tolerability of the D1 Dopamine Receptor Antagonist Ecopipam in Patients With Lesch-Nyhan Disease,” <https://clinicaltrials.gov/study/NCT01065558?term=NCT01065558%…
[cited by applicant]
Clinical Trials—NCT04007991, Results Posted, “Ecopipam Tablets to Study Tourette's Syndrome in Children and Adolescents (D1AMOND)” <https://clinicaltrials.gov/study/NCT04007991?term=NCT04007991&rank=1&tab=results> (post…
[cited by applicant]
Clinical Trials—NCT04007991, Study Details, “Ecopipam Tablets to Study Tourette's Syndrome in Children and Adolescents (D1AMOND),” <https://clinicaltrials.gov/study/NCT04007991?term=NCT04007991&rank=1&a=10> (posted Oct.…
[cited by applicant]
Clinical Trials—NCT01065558, Results Posted, “Safety and Tolerability of the D1 Dopamine Receptor Antagonist Ecopipam in Patients With Lesch-Nyhan Disease,” <https://clinicaltrials.gov/study/NCT01065558?term=NCT01065558…
[cited by applicant]
Clinical Trials—NCT01215357, Results Posted, “Clinical Study to Determine if Ecopipam Can Reduce Urges to Gamble,” <https://clinicaltrials.gov/study/NCT01215357?term=NCT01215357&rank=1&a=7&tab=results> (posted May 14, 2…
[cited by applicant]
Clinical Trials—NCT01215357, Study Details, “Clinical Study to Determine if Ecopipam Can Reduce Urges to Gamble,” <https://clinicaltrials.gov/study/NCT01215357?term=NCT01215357&rank=1&a=7> (posted May 14, 2024).
[cited by applicant]
Clinical Trials—NCT01244633, Results Posted, “Ecopipam Treatment of Tourette Syndrome,” <https://clinicaltrials.gov/study/NCT01244633?term=NCT01244633&rank=1&tab=results> (posted Sep. 29, 2015).
[cited by applicant]
Clinical Trials—NCT01244633, Study Details, “Ecopipam Treatment of Tourette Syndrome,” <https://clinicaltrials.gov/study/NCT01244633?term=NCT01244633&rank=1> (posted Sep. 29, 2015).
[cited by applicant]
Clinical Trials—NCT01751802, Results Posted, “Ecopipam Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease,” <https://clinicaltrials.gov/study/NCT01751802?term=NCT01751802&rank=1 &tab=results> (pos…
[cited by applicant]
Clinical Trials—NCT01751802, Study Details, “Ecopipam Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease,” <https://clinicaltrials.gov/study/NCT01751802?term=NCT01751802&rank=1> (posted Apr. 22, 2…
[cited by applicant]
Clinical Trials—NCT02102698, Study Details, “Ecopipam Treatment of Tourette's Syndrome in Subjects 7-17 Years,” <https://clinicaltrials.gov/study/NCT02102698?term=NCT02102698&rank=1&a=12> (posted Apr. 19, 2024).
[cited by applicant]
Clinical Trials—NCT02909088, Study Details, “Efficacy and Tolerability of Ecopipam in Adults With Childhood Onset Fluency Disorder (Stuttering).” <https://clinicaltrials.gov/study/NCT02909088?term=NCT02909088&rank=1&a=2…
[cited by applicant]
Clinical Trials—NCT03218969, Study Details, “Treatment of Restless Leg Syndrome (RLS) Augmentation With Ecopipam, a D1 Specific Antagonist (RLS-Ecopipam),” <https://clinicaltrials.gov/study/NCT03218969?term=NCT03218969&…
[cited by applicant]
Clinical Trials—NCT04114539, Results Posted, “Ecopipam Tablets to Study Tourette Syndrome in Children and Adolescents—Open Label Extension,” <https://clinicaltrials.gov/study/NCT04114539?term=NCT04114539&rank=1&tab=resu…
[cited by applicant]
Clinical Trials—NCT04114539, Study Details, “Ecopipam Tablets to Study Tourette Syndrome in Children and Adolescents—Open Label Extension,” <https://clinicaltrials.gov/study/NCT04114539?term=NCT04114539&rank=1> (posted …
[cited by applicant]
Clinical Trials—NCT04492956, Results Posted, “Effects of Ecopipam or Placebo in Adults With Stuttering (Speak Freely),” <https://clinicaltrials.gov/study/NCT04492956?term=NCT04492956&rank=1&a=11&tab=results> (posted Apr…
[cited by applicant]
Clinical Trials—NCT04492956, Study Details, “Effects of Ecopipam or Placebo in Adults With Stuttering (Speak Freely),” <https://clinicaltrials.gov/study/NCT04492956?term=NCT04492956&rank=1> (posted Apr. 28, 2022).
[cited by applicant]
Clinical Trials—NCT04764851, Study Details, “Drug-Drug Interaction Study to Evaluate the Effects of Ecopipam on the Pharmacokinetics of Multiple Substrates,” <https://clinicaltrials.gov/study/NCT04764851?term=NCT0476485…
[cited by applicant]
Clinical Trials—NCT04881955, Study Details, “Study of the Absorption, Metabolism, and Excretion of [14C]-Ecopipam in Healthy Male Subjects,” <https://clinicaltrials.gov/study/NCT04881955?term=NCT04881955&rank=1> (posted…
[cited by applicant]
Clinical Trials—NCT05334108, Study Details, “Drug-Drug Interaction Study to Evaluate the Effects of Ecopipam on the Pharmacokinetics of Multiple Substrates for Drug Metabolism and Transport,” <https://clinicaltrials.gov…
[cited by applicant]
Clinical Trials—NCT05615220, Results Posted “Ecopipam Tablets to Study Tourette's Disorder in Children, Adolescents and Adults (D1AMOND),” <https:///clinicaltrials.gov/study/NCT05615220?term=NCT05615220&rank=1&tab=resul…
[cited by applicant]
Clinical Trials—NCT05615220, Study Details, “Ecopipam Tablets to Study Tourette's Disorder in Children, Adolescents and Adults (D1AMOND),” <https://clinicaltrials.gov/study/NCT05615220?term=NCT05615220&rank=1> (Version …
[cited by applicant]
Clinical Trials—NCT06021522, Study Details, “A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette's Disorder,” <https://clinicaltrials.gov/study/NCT06021522?term=NCT…
[cited by applicant]
Clinical Trials—NCT06669091, Study Details, “Food-effect Study of Ecopipam Pharmacokinetics,” <https://clinicaltrials.gov/study/NCT06669091?term=NCT06669091&rank=1> (posted Jan. 27, 2025).
[cited by applicant]
Cunniff et al., Design of a Confirmatory Trial of Ecopipam in Tourette Syndrome, American Academy of Neurology, Poster 011, 1 Page (Apr. 2023).
[cited by applicant]
Cunniff et al., Design of a Phase 3 Maintenance-of-Effect Trial of Ecopipam in Tourette Syndrome, 15th European Conference on Tourette Syndrome, Poster 15, 1 Page (Jun. 2023).
[cited by applicant]
Dubow et al., Ecopipam, a Selective D1 Antagonist in Development for the Treatment of Tourette Syndrome in Children and Adolescents: the Phase 2b D1AMOND Study Design, International Congress of Parkinson's Disease and M…
[cited by applicant]
Freidy et al., Increasing Ecopipam Exposure Improves Yale Global Tic Severity Scale-Total Tic Scores in Children and Adolescents With Tourette Syndrome: Results From a Population Pharmacokinetic Model-Based Simulation U…
[cited by applicant]
Freidy et al., Population Pharmacokinetics of Ecopipam and Active Metabolite (EBS-101-40853) in Healthy Volunteers and Pediatric Patients With Tourette Syndrome, Poster W-048, 1 Page (Nov. 2023).
[cited by applicant]
Gilbert et al., Ecopipam Does Not Adversely Affect Metabolic Parameters in Pediatric Patients With Tourette Syndrome: Results From a Phase 2b Randomized, Placebo-Controlled Trial With a 12-Month Open-Label Extension, Ch…
[cited by applicant]
Gilbert et al., Ecopipam Does Not Adversely Affect Metabolic Parameters in Pediatric Subjects With Tourette Syndrome: Results From a Phase 2b With 12-Month Open-Label Extension Study, International Congress of Parkinson…
[cited by applicant]
Gilbert et al., Effect of Ecopipam, a Selective Dopamine-1 Receptor Antagonist, on Tic Characteristics as Assessed by the YGTSS: Results From the Phase 2b (D1AMOND) Randomized, Double-Blind, Placebo-Controlled Clinical …
[cited by applicant]
Gilbert et al., Effect of Ecopipam, a Selective Dopamine-1 Receptor Antagonist, on Tic Characteristics as Assessed by the YGTSS: Results From the Phase 2b Randomized, Double-Blind, Placebo-Controlled Clinical Trial in T…
[cited by applicant]
Gilbert et al., Effect of Ecopipam, a Selective Dopamine-1 Receptor Antagonist, on Tic Characteristics as Assessed by YGTSS: Results From the Phase 2b (D1AMOND) Randomized, Double-Blind, Placebo-Controlled Clinical Tria…
[cited by applicant]
Gilbert et al., Long-Term Safety and Durability of Effect of Ecopipam in Pediatric Patients With Tourette Syndrome: Results of a 12-Month Open-Label Extension Study, International Congress of Parkinson's Disease and Mov…
[cited by applicant]
Gilbert et al., Safety and Effect of 12-Month Ecopipam Treatment in Pediatric Patients with Tourette Syndrome, Movement Disorders Clinical Practice, 12(8):1157-1166 (May 2025).
[cited by applicant]
Gilbert et al., Safety and Tolerability of Ecopipam in Tourette Syndrome With Psychiatric Comorbidities, American Academy of Neurology Annual Meeting, Poster 001, 1 Page (Apr. 2024).
[cited by applicant]
Gilbert et al., Safety and Tolerability of Ecopipam in Tourette Syndrome With Psychiatric Comorbidities, International Congress of Parkinson's Disease and Movement Disorders, Poster 631, 1 Page (Oct. 2024).
[cited by applicant]
Gilbert et al., Safety and Tolerability of Ecopipam in Tourette Syndrome With Psychiatric Comorbidities, Neurology, 102(7):12 Pages (Apr. 2024).
[cited by applicant]
Gilbert, From D1 Receptors to Tic Reduction: Results From the Phase III Study of Ecopipam for Tourette Syndrome, European Society for the Study of Tourette, 70 Pages (2025).
[cited by applicant]
Isaacs et al., Clinical Profile of Children and Adolescents Newly Diagnosed With Tourette Syndrome: Observational Cohort Study of a Large Electronic Health Records Database, American Academy of Neurology, Poster 6-005, …
[cited by applicant]
Mahableshwarkar et al., Ecopipam in Children and Adolescents with Tourette Syndrome: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 2b Study, American Academy of Neurology, 1 page (Apr. 2022).
[cited by applicant]
Mahableshwarkar et al., Randomized, Double-Blind, Placebo-Controlled Phase 2b Study of Ecopipam in Children and Adolescents With Tourette Syndrome, APA 2022 Annual Meeting, Poster P6-019, 1 page (May 2022).
[cited by applicant]
McGuire et al., An Anchor-Based Method to Establish Clinically Meaningful Changes in YGTSS-TTS Using Data From the Phase 2b and Safety Extension Studies of Ecopipam, a Selective D1 Receptor Antagonist, in Tourette Syndr…
[cited by applicant]
McGuire et al., Changes in Metabolic Parameters and Determination of Minimal Clinically Important Difference in YGTSS-TTS Using Data From the Randomized Phase 2b and Open-Label Extension Studies of Ecopipam for Tourette…
[cited by applicant]
McGuire et al., Determining Clinically Meaningful Improvement in Children and Adolescents with Tourette Syndrome Receiving Pharmacotherapy, Journal of Child and Adolescent Psychopharmacology, 35(8):447-453 (Oct. 2025).
[cited by applicant]
Schmith et al., Evaluation of the Effect of CYP3A4 and P-Glycoprotein Inhibition by Itraconazole or Induction by Rifampicin on the Pharmacokinetics of Ecopipam and its Metabolites, American Society for Clinical Pharmaco…
[cited by applicant]
Schmith et al., Metabolic Profiling of Ecopipam, American Society for Clinical Pharmacology and Therapeutics, Poster PII-123, 1 Page (Mar. 2024).
[cited by applicant]
Schmith et al., Microdosing Approach to Evaluate Whether Ecopipam Affects Drug Metabolism and Transport of Concomitant Medications, American Society for Clinical Pharmacology and Therapeutics Poster PII-125, 1 Page (Mar…
[cited by applicant]
Schmith et al., The Effect of UGT Inhibition on the Pharmacokinetics of Ecopipam and its Metabolite, American Society for Clinical Pharmacology and Therapeutics, Poster PII-088, 1 Page (Mar. 2023).
[cited by applicant]
Tomczak et al., High Rates of Discontinuation of D2 Receptor Antagonists as Treatment of Tourette Syndrome in Children: A Retrospective Database Analysis, American Academy of Neurology, Poster 6-001, 1 Page (Apr. 2025).
[cited by applicant]
Wanaski et al., Effects of Ecopipam on Growth and Development in Juvenile Rats, American Academy of Neurology, Poster 010, 1 Page (Apr. 2024).
[cited by applicant]
Wanaski et al., The Effect of Ecopipam and Its Metabolites on Cardiac Repolarization, QTcF, American Academy of Neurology Annual Meeting, Poster 5-014, 1 Page (Apr. 2025).
[cited by applicant]