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 and between 20 mg and 200 mg trospium chloride to the patient during a 24-hour period. The central nervous system disorder is 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.
1. A single capsule formulation for oral administration comprising xanomeline and/or a salt thereof in an amount to cause a side effect chosen from nausea, vomiting, diarrhea, sweating and excess salivation; and trospium chloride in an amount effective to reduce the side effect associated with the oral administration of the xanomeline and/or the salt thereof.
2. The formulation of claim 1 , which is formulated as an immediate release formulation.
3. The formulation of claim 1 , which is formulated as a controlled release formulation.
4. The formulation of claim 1 , wherein the xanomeline and/or the salt thereof is formulated as a controlled release formulation and the trospium chloride is formulated as an immediate release formulation.
5. The formulation of claim 1 , wherein the formulation contains from 1 milligram to 1 gram of xanomeline and/or the salt thereof.
6. The formulation of claim 1 , wherein the formulation contains from five milligrams to 700 milligrams of xanomeline and/or the salt thereof.
7. The formulation of claim 1 , wherein the formulation contains from five milligrams to 500 milligrams of xanomeline and/or the salt thereof.
8. The formulation of claim 1 , wherein the formulation contains from 25 milligrams to 300 milligrams of xanomeline and/or the salt thereof.
9. The formulation of claim 1 , wherein the formulation contains from one milligram to 400 milligrams of trospium chloride.
10. The formulation of claim 1 , wherein the formulation contains from 6.5 milligrams to 200 milligrams of trospium chloride.
11. The formulation of claim 1 , wherein the formulation contains 20 milligrams of trospium chloride.
12. A method of treating schizophrenia in a patient in need thereof, the method comprising:
orally administering a single capsule formulation of claim 1 twice daily.
13. The method of claim 12 , wherein the formulation contains 20 milligrams of trospium chloride.
14. The method of claim 12 , wherein the formulation contains from 25 milligrams to 300 milligrams of xanomeline and/or the salt thereof.
15. The formulation of claim 1 , wherein the salt of xanomeline is the salt of tartaric acid.
16. The formulation of claim 1 , wherein the amount of the xanomeline and/or the salt thereof is effective to treat a central nervous system disorder chosen from Alzheimer's disease, Huntington's disease, Parkinson's disease, and Lewy Body dementia.