Pharmaceutical compositions comprising 4-(6Br,10aS)-3-methyl-2, 3, 6b, 9, 10, 10a-hexahydro-1H, 7H-pyrido[3′, 4′, 5] pyrolo[1,2,3-de] quinoxalin-8YL)-1-(4-fluorophenyl)-butane-1-one and methods of treating conditions of the central nervous system
The invention relates to pharmaceutical compositions comprising, compounds of Formula Q: wherein W is —N(H)—, or —N(CH 3 )—, and Y is —C(═O)— or —O—, in free base or pharmaceutically acceptable salt form, and methods of use in the treatment of diseases involving 5-HT 2A receptor, serotonin transporter (SERT) pathway and/or the dopamine D 2 receptor pathway, and methods of treating conditions of the central nervous system therewith.
1. A method for: (a) inhibiting serotonin 5-hydroxytryptamine-2A receptor activity in a patient, (b) inhibiting serotonin reuptake transporter activity in a patient, or (c) modulating dopamine D2 receptor function in a patient, wherein the method comprises administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising:
(i) a compound of Formula Q:
wherein:
W is —N(CH 3 )—; and
Y is —C(═O)—;
in free base or pharmaceutically acceptable salt form;
(ii) a polymeric matrix comprising one or more polymers selected from the group consisting of a poly(lactic acid) polymer, a poly(glycolic acid) polymer, and a poly(D,L-lactide-co-glycolide) polymer;
(iii) a pharmaceutically acceptable diluent or carrier; and
(iv) optionally a vehicle comprising a viscosity enhancing agent.
2. The method according to claim 1 , wherein the patient has a disorder involving the serotonin 5-hydroxytryptamine-2A receptor pathway, the serotonin reuptake transporter pathway, and/or the dopamine D2 receptor pathway selected from the group consisting of (1) psychosis in a patient suffering from depression, (2) depression in a patient suffering from psychosis, (3) a mood disorder associated with psychosis, and (4) a sleep disorder associated with psychosis.
3. The method according to claim 1 , wherein the patient has a disorder involving the serotonin 5-hydroxytryptamine-2A receptor pathway, the serotonin reuptake transporter pathway, and/or the dopamine D2 receptor pathway selected from the group consisting of an agitation in autism, an agitation in a related autistic disorder, an agitation in dementia, anxiety, depression, migraine, obesity, psychosis, schizophrenia, a condition associated with cephalic pain, a gastrointestinal disorder, a sexual disorder, a sleep disorder, and a social phobia.
4. The method according to claim 3 , wherein the disorder is depression.
5. The method according to claim 3 , wherein the disorder is psychosis.
6. The method according to claim 3 , wherein the disorder is schizophrenia.
7. The method according to claim 1 , wherein the compound of Formula Q is in pharmaceutically acceptable salt form.
8. The method according to claim 7 , wherein the pharmaceutically acceptable salt form is a toluenesulfonic acid addition salt form.
9. The method according to claim 8 , wherein the polymeric matrix comprises a poly(D,L-lactide-co-glycolide) polymer.
10. The method according to claim 9 , wherein the polymeric matrix is a microspheric polymeric matrix comprising a biodegradable poly(D,L-lactide-co-glycolide) polymer.
11. The method according to claim 1 , wherein the compound of Formula Q is either dissolved in the polymeric matrix or dispersed in the polymeric matrix.
12. The method according to claim 1 , wherein the pharmaceutical composition is non-aqueous and the pharmaceutically acceptable diluent or carrier is an organic solvent.
13. The method according to claim 12 , wherein the pharmaceutically acceptable diluent or carrier is a water-miscible organic solvent.
14. The method according to claim 1 , wherein the pharmaceutical composition comprises a vehicle comprising a viscosity enhancing agent, and wherein the viscosity enhancing agent is sodium carboxymethylcellulose.
15. The method according to claim 1 , wherein the pharmaceutical composition is formulated as a sustained-release and/or delayed release injectable composition.
16. The method according to claim 15 , wherein the compound of Formula Q is in pharmaceutically acceptable salt form.
17. The method according to claim 16 , wherein the pharmaceutically acceptable salt form is a toluenesulfonic acid addition salt form.
18. The method according to claim 17 , wherein the polymeric matrix comprises a poly(D,L-lactide-co-glycolide) polymer.
19. The method according to claim 18 , wherein the polymeric matrix is a microspheric polymeric matrix comprising a biodegradable poly(D,L-lactide-co-glycolide) polymer.