Methods and compositions for sleep disorders and other disorders

Abstract

Use of particular substituted heterocycle fused gamma-carboline compounds as pharmaceuticals and pharmaceutical compositions comprising them for the treatment of one or more disorders involving the 5-HT2A, SERT and/or dopamine D2 pathways are disclosed. In addition, the compounds may be combined with other therapeutic agents for the treatment of one or more sleep disorders, depression, psychosis, dyskinesias, and/or Parkinson’s disease or any combinations.

1 - 39 . (canceled) 
     
     
         40 . A method for modulating dopamine receptor activity, inhibiting serotonin transporter activity, and/or inhibiting 5-HT 2A  receptor activity, in a patient in need thereof, comprising administering to a patient in need thereof an effective amount of a Compound of Formula I
                     
 wherein X is O, —NH or —N(CH 
 3 ); and Y is —O— or —C(O)—; in free base or pharmaceutically acceptable salt form. 
     
     
         41 . The method according to  claim 40 , wherein the Compound of Formula I is selected from the group consisting of:
                                                                                                                                     in free base or pharmaceutically acceptable salt form.   
     
     
         42 . The method according to  claim 40 , wherein the Compound of Formula I is
                       in free base or pharmaceutically acceptable salt form.   
     
     
         43 . The method according to  claim 40 , wherein the compound is in pharmaceutically acceptable salt form. 
     
     
         44 . The method according to  claim 43 , wherein the salt form is an acid addition salt with an acid selected from the group consisting of an acid addition salt acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, and isethionic acid. 
     
     
         45 . The method according to  claim 44 , wherein the salt form is a toluenesulfonic acid addition salt. 
     
     
         46 . The method according to  claim 45 , wherein the salt is a crystalline salt. 
     
     
         47 . The method according to  claim 46 , wherein the salt is an amorphous salt. 
     
     
         48 . The method according to  claim 40 , wherein the Compound of Formula I is
                       in toluenesulfonic acid addition salt form.   
     
     
         49 . The method according to  claim 48 , wherein the salt is a crystalline salt. 
     
     
         50 . The method according to  claim 48 , wherein the salt is an amorphous salt. 
     
     
         51 . The method according to  claim 40 , wherein the method modulates dopamine receptor protein phosphorylation. 
     
     
         52 . The method according to  claim 40 , wherein the method does not result in side effects resulting from activity at the adrenergic alpha-1a receptor, serotonin 5-HT2C receptor, or histamine H1 receptor. 
     
     
         53 . The method according to  claim 40 , wherein the effective amount is an amount sufficient to bind to SERT, 5-HT2A, and D2 receptors with a Ki of less than 100 nM. 
     
     
         54 . The method according to  claim 40 , wherein the effective amount is an amount sufficient to bind to SERT, 5-HT2A, and D2 receptors with a Ki of less than 100 nM. 
     
     
         55 . The method according to  claim 40 , wherein the effective amount is 1 mg to 100 mg, calculated as the equivalent amount of free base. 
     
     
         56 . The method according to  claim 40 , wherein the effective amount is 2.5 mg to 50 mg, calculated as the equivalent amount of free base. 
     
     
         57 . The method according to  claim 55 , wherein the effective amount is administered daily as a single unit dose. 
     
     
         58 . The method according to  claim 40 , wherein the patient suffers from depression, schizophrenia, bipolar disorder, psychosis, dyskinesia, sleep disorder, or Parkinson’s disease. 
     
     
         59 . The method according to  claim 58 , wherein the method is effective to treat the patient’s depression, schizophrenia, bipolar disorder, psychosis, dyskinesia, sleep disorder, or Parkinson’s disease. 
     
     
         60 . The method according to  claim 58 , wherein the patient suffers from depression, schizophrenia, or bipolar disorder, and the method is effective in treating said depression, schizophrenia, or bipolar disorder.