Methods and compositions for treatment of disorders ameliorated by muscarinic receptor activation

Abstract

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.