METHODS AND COMPOSITIONS FOR TREATMENT OF DISORDERS AMELIORATED BY MUSCARINIC RECEPTOR ACTIVATION

• US 20110020423A1
• Filed: 07/21/2010
• Published: 01/27/2011
• Est. Priority Date: 07/22/2009
• Status: Abandoned Application

• Current Assignee: Puretech Management, Inc. (PureTech Health Plc)
• Original Assignee: Puretech Ventures LLC
• Inventors: Miller, Andrew C., Murray, Philip E. III, Elenko, Eric
• Application Number:
  US12/840,980
• Publication Number:
  US 20110020423A1
• Time in Patent Office: Days
• US Class Current: 424/432
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/222 with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/26 : Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence

Abstract

Methods for the treatment of CNS disorders using combinations of muscarinic activators and inhibitors, and medicaments comprising muscarinic activators and inhibitors.

Claims

1. A method of treating a central nervous system disorder comprising:

administering to a patient a muscarinic Activator with a muscarinic Inhibitor, wherein the central nervous system disorder is selected from schizophrenia, Disorders Related To Schizophrenia, Muscarinic Disorder, Movement Disorder, Mood Disorder, Cognitive Disorder, Attention Disorder, and Addictive Disorder.

3. The method according to claim 1 or claim 2, wherein the combination of the muscarinic Activator and the muscarinic Inhibitor has a theta score of less than 149.

4. The method according to claim 1 or claim 2, wherein the combination of the muscarinic Activator and the muscarinic Inhibitor has a theta score of greater than 150.

5. The method according to claim 1 or claim 2, wherein the combination of the muscarinic Activator and the muscarinic Inhibitor has a theta score of greater than 200.

6. The method according to claim 1 or claim 2, wherein the combination of the muscarinic Activator and the muscarinic Inhibitor has a theta score of greater than 230.

7. The method according to claim 1 or claim 2, wherein the muscarinic Activator is administered consecutively with the muscarinic Inhibitor.

8. The method according to claim 1 or claim 2, wherein the muscarinic Inhibitor and the muscarinic Activator are administered simultaneously.

9. The method according to claim 1 or claim 2, wherein from 10 micrograms to 10 grams of the muscarinic Activator is administered.

10. The method according to claim 1 or claim 2, wherein from 1 milligram to 1 gram of the muscarinic Activator is administered.

11. The method according to claim 1 or claim 2, wherein from 10 micrograms to 10 grams of the muscarinic Inhibitor is administered.

12. The method according to claim 1 or claim 2, wherein from 1 milligram to 1 gram of the muscarinic Inhibitor is administered.

13. The method according to claim 1 or claim 2, wherein the muscarinic Activator and the muscarinic Inhibitor are packaged in one dosage vehicle.

14. The method of claim 13, wherein the dosage vehicle is selected from a tablet, troche, liquid, emulsion, suspension, drops, capsule, gel cap, cream, gel, ointment, foam, cream, aerosol, suppository, enema, and vaginal ring.

15. The method according to claim 1 or claim 2, wherein the muscarinic Activator and the muscarinic Inhibitor are packaged in separate dosage vehicles independently selected from a tablet, troche, liquid, emulsion, suspension, drops, capsule, gel cap, cream, gel, ointment, foam, cream, aerosol, suppository, enema, and vaginal ring.

16. The method according to claim 1 or claim 2, wherein the muscarinic Activator and the muscarinic Inhibitor are formulated in an immediate release formulation.

17. The method according to claim 1 or claim 2, wherein the muscarinic Activator and the muscarinic Inhibitor are formulated in a controlled release formulation.

18. The method according to claim 1 or claim 2, wherein the muscarinic Activator and the muscarinic Inhibitor are administered in combination with a therapeutic agent.

19. The method of claim 18, wherein the therapeutic agent is selected from an antipsychotic, an anxiolytic, an anti-depressant, a sedative, a tranquilizer, and combinations thereof.

2. A method of decreasing a side effect induced by a muscarinic Activator in a patient, comprising administering to the patient a muscarinic Inhibitor.

20. A medicament comprising a muscarinic Activator, a muscarinic Inhibitor, and a pharmaceutically acceptable carrier.

21. The medicament of claim 20, wherein the combination of the muscarinic Activator and the muscarinic Inhibitor has a theta score of less than 149.

22. The medicament of claim 20, wherein the combination of the muscarinic Activator and the muscarinic Inhibitor has a theta score of greater than 150.

23. The medicament of claim 20, wherein the combination of the muscarinic Activator and the muscarinic Inhibitor has a theta score of greater than 200.

24. The medicament of claim 20, wherein the combination of the muscarinic Activator and the muscarinic Inhibitor has a theta score of greater than 230.

25. The medicament of claim 20, comprising from 10 micrograms to 10 grams of the muscarinic Activator.

26. The medicament of claim 20, comprising from 1 milligram to 1 gram of the muscarinic Activator.

27. The medicament of claim 20, comprising from 10 micrograms to 10 grams of the muscarinic Inhibitor.

28. The medicament of claim 20, comprising from 1 milligram to 1 gram of the muscarinic Inhibitor.

29. The medicament of claim 20, 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.

30. The medicament of claim 20, which is formulated as an immediate release formulation.

31. The medicament of claim 20, which is formulated as a controlled release formulation.