METHODS AND COMPOSITIONS FOR TREATMENT OF DISORDERS AMELIORATED BY MUSCARINIC RECEPTOR ACTIVATION
The present disclosure provides a method of treating a central nervous system disorder in a patient in need thereof. The method comprises orally administering between 75 mg and 300 mg xanomeline salt and between 20 mg and 200 mg trospium chloride to the patient during a 24-hour period, the central nervous system disorder being selected from schizophrenia, Alzheimer's disease, Huntington's disease, Parkinson's disease, and Lewy Body dementia, wherein use of the trospium chloride alleviates a side effect associated with use of the xanomeline salt.
1 - 31 . (canceled)
32 . A medicament comprising a combination of a muscarinic activator and a muscarinic inhibitor chosen from:
xanomeline and/or a salt thereof and trospium chloride;
sabcomeline and/or a salt thereof and trospium chloride;
milameline and/or a salt thereof and trospium chloride;
xanomeline and/or a salt thereof and tolterodine and/or a salt thereof;
milameline and/or a salt thereof and tolterodine and/or a salt thereof;
sabcomeline and/or a salt thereof and trospium chloride controlled release;
xanomeline and/or a salt thereof and trospium chloride controlled release;
milameline and/or a salt thereof and trospium chloride controlled release;
xanomeline and/or a salt thereof and darifenacin and/or a salt thereof;
xanomeline and/or a salt thereof and solifenacin and/or a salt thereof;
sabcomeline and/or a salt thereof and solifenacin and/or a salt thereof;
talsaclidine and/or a salt thereof and trospium chloride;
cevimeline and/or a salt thereof and trospium chloride;
talsaclidine and/or a salt thereof and darifenacin and/or a salt thereof;
talsaclidine and/or a salt thereof and solifenacin and/or a salt thereof;
talsaclidine and/or a salt thereof and trospium chloride controlled release;
talsaclidine and/or a salt thereof and tolterodine and/or a salt thereof;
xanomeline and/or a salt thereof and fesoterodine and/or a salt thereof;
cevimeline and/or a salt thereof and darifenacin and/or a salt thereof; and
cevimeline and/or a salt thereof and trospium chloride controlled release; and
a pharmaceutically acceptable carrier.
33 . The medicament of claim 32 , wherein use of the muscarinic inhibitor alleviates a side effect associated with use of the muscarinic activator.
34 . The medicament of claim 32 , wherein the combination of a muscarinic activator and a muscarinic inhibitor is xanomeline and/or the salt thereof and trospium chloride.
35 . The medicament of claim 32 , wherein the combination of the muscarinic activator and the muscarinic inhibitor has a theta score greater than 230.
36 . The medicament of claim 32 , comprising from 10 micrograms to 10 grams of the muscarinic activator.
37 . The medicament of claim 32 , comprising from 1 milligram to 1 gram of the muscarinic activator.
38 . The medicament of claim 32 , comprising from 10 micrograms to 10 grams of the muscarinic inhibitor.
39 . The medicament of claim 32 , comprising from 1 milligram to 1 gram of the muscarinic inhibitor.
40 . The medicament of claim 32 , comprising from 1 milligram to 1 gram of the muscarinic activator and from 1 milligram to 1 gram of the muscarinic inhibitor.
41 . The medicament of claim 32 , comprising from 25 to 300 milligrams of xanomeline and/or the salt thereof.
42 . The medicament of claim 32 , comprising from 6.5 to 200 milligrams of trospium chloride.
43 . The medicament of claim 32 , which is in the form of a tablet, troche, liquid, emulsion, suspension, drops, capsule, gel cap, cream, gel, ointment, foam, cream, aerosol, suppository, enema or vaginal ring.
44 . The medicament of claim 32 , which is formulated as an immediate release formulation.
45 . The medicament of claim 32 , which is formulated as a controlled release formulation.
46 . The medicament of claim 32 , wherein the muscarinic activator is formulated as a controlled release formulation and the muscarinic inhibitor is formulated as an immediate release formulation.
47 . A method for treating a central nervous system disorder chosen from schizophrenia, disorders related to schizophrenia, muscarinic disorder, movement disorder, mood disorder, cognitive disorder, attention disorder, and addictive disorder in a patient in need thereof, comprising administrating the oral medicament of claim 32 to the patient in need thereof
48 . The method of claim 47 , wherein the central nervous system disorder is schizophrenia.
49 . The method of claim 47 , wherein the central nervous system disorder is Alzheimer's disease.
50 . The method of claim 47 , wherein the central nervous system disorder is Huntington's disease.
51 . The method of claim 47 , wherein the central nervous system disorder is Parkinson's disease.
52 . The method of claim 47 , wherein the central nervous system disorder is Lewy Body dementia
53 . The method of claim 47 , wherein the muscarinic activator and the muscarinic inhibitor are in the same dosage vehicle.
54 . The method of claim 47 , wherein the muscarinic activator and the muscarinic inhibitor are in different dosage vehicles.
55 . The method of claim 47 , wherein between 20 mg and 60 mg of trospium chloride is administered to the patient during the 24-hour period.
56 . The method of claim 47 , wherein between 60 and 200 mg trospium chloride is administered to the patient during the 24-hour period.
57 . The method of claim 47 , wherein the xanomeline is the salt of tartaric acid.