Dextromethorphan and an oxidase inhibitor for treating intractable conditions

• US 5,863,927 A
• Filed: 09/19/1996
• Issued: 01/26/1999
• Est. Priority Date: 09/22/1994
• Status: Expired

• Current Assignee: Avanir Pharmaceuticals, Inc. (Otsuka Holdings Company Limited)
• Original Assignee: Center for Neurologic Study
• Inventors: Smith, Richard Alan, Licht, Jonathan M.
• Primary Examiner(s): Spivack, Phyllis G.
• Application Number:
  US08/464,792
• Time in Patent Office: 859 Days
• Field of Search: 514/289, 514/305, 514/491, 514/652, 514/654, 514/649, 514/651
• US Class Current: 514/289
• 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 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/49 Cinchonan derivatives, e.g. quinine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Methods are disclosed for increasing the effectiveness of dextromethorphan in treating chronic or intractable pain, for treating tinnitus and for treating sexual dysfunction comprising administering dextromethorphan in combination with a therapeutically effective dosage of a debrisoquin hydroxylase inhibitor. A preferred combination is dextromethorphan and the oxidative inhibitor quinidine.

Claims

1. A method of increasing the effectiveness of dextromethorphan in treating chronic or intractable pain, comprising administering to a patient suffering from chronic or intractable pain a therapeutically effective dosage of dextromethorphan or a pharmaceutically acceptable salt thereof, in combination with a therapeutically effective dosage of a debrisoquin hydroxylase inhibitor.

2. The method of claim 1 wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of quinidine, quinine, and pharmaceutically acceptable salts thereof.

3. The method of claim 2 wherein quinidine is administered at a dosage not exceeding about 300 milligrams per day.

4. The method of claim 1 wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of disulfiram, fluoxetine, propranolol, nortriptyline, and pharmaceutically acceptable salts thereof.

5. A method of using dextromethorphan to treat chronic or intractable pain, comprising administering, to a patient suffering from chronic or intractable pain, dextromethorphan or a pharmaceutically acceptable salt thereof in combination with a debrisoquin hydroxylase inhibitor, wherein the dextromethorphan or salt thereof and the inhibitor are administered at combined dosages which render the dextromethorphan therapeutically effective in substantially reducing chronic or intractable pain, without causing unacceptable side effects.

6. The method of claim 5 wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of quinidine, quinine, and pharmaceutically acceptable salts thereof.

7. The method of claim 6 wherein quinidine is administered at a dosage not exceeding about 300 milligrams per day.

8. The method of claim 5 wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of disulfiram, fluoxetine, propranolol, nortriptyline, and pharmaceutically acceptable salts thereof.

9. A method of using dextromethorphan in treating tinnitus, comprising administering, to a patient suffering from tinnitus, dextromethorphan or a pharmaceutically acceptable salt thereof in combination with a debrisoquin hydroxylase inhibitor, wherein the dextromethorphan or salt thereof and the debrisoquin hydroxylase inhibitor are administered at combined dosages which render the dextromethorphan thereof therapeutically effective in substantially reducing tinnitus without causing unacceptable side effects.

10. The method of claim 9 wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of quinidine, quinine, and pharmaceutically acceptable salts thereof.

11. The method of claim 10 wherein quinidine is administered at a dosage not exceeding about 300 milligrams per day.

12. The method of claim 9 wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of disulfiram, fluoxetine, propranolol, nortriptyline, and pharmaceutically acceptable salts thereof.

13. A method for treating sexual dysfunction, comprising administering to a patient in need thereof dextromethorphan or a pharmaceutically acceptable salt thereof in combination with a debrisoquin hydroxylase inhibitor, at combined dosages which render the dextromethorphan thereof therapeutically effective in treating the sexual dysfunction.

14. The method of claim 13 wherein the patient is a male who suffers from priapism or premature ejaculation.

15. The method of claim 13 wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of quinidine, quinine, and pharmaceutically acceptable salts thereof.

16. The method of claim 15 wherein quinidine is administered at a dosage not exceeding about 300 milligrams per day.

17. The method of claim 13 wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of disulfiram, fluoxetine, propranolol, nortriptyline, and pharmaceutically acceptable salts thereof.

18. A unit dosage formulation for treatment of chronic or intractable pain, comprising:

(a) dextromethorphan or a pharmaceutically acceptable salt thereof, and,

(b) a debrisoquin hydroxylase inhibitor, in a combined form that is designed for oral ingestion by humans, wherein the dextromethorphan or salt thereof and the debrisoquin hydroxylase inhibitor are present at a combined dosage which renders the dextromethorphan therapeutically effective in substantially reducing chronic or intractable pain, without causing unacceptable side effects.

19. The unit dosage formulation of claim 18, comprising a digestible capsule which encloses the dextromethorphan or pharmaceutically acceptable salt thereof and the debrisoquin hydroxylase inhibitor.

20. The unit dosage formulation of claim 18, wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of quinidine, quinine, and pharmaceutically acceptable salts thereof.

21. The unit dosage formulation of claim 20, wherein the dosage of quinidine is 300 milligrams/day or less.

22. The unit dosage formulation of claim 18, wherein the debrisoquin hydroxylase inhibitor is selected from the group consisting of disulfiram, fluoxetine, propranolol, nortriptyline, and pharmaceutically acceptable salts thereof.