Dextromethorphan and an oxidase inhibitor for treating intractable conditions

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.

We claim:  
     
       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 formation 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.