Pharmaceutical composition and method for treating hypertension

Abstract

Dextromethorphan is used to lower blood pressure in a subject suffering from hypertension, alone or in combination with another anti-hypertensive agent. In particular, dextromethorphan acts synergistically with a calcium channel blocker, such as amlodipine, to result in a major improvement in the treatment of hypertension, with no or little adverse effects.

1 . A method of treating hypertension or a symptom associated therewith in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of dextromethorphan and a pharmaceutically acceptable carrier. 
     
     
         2 . The method of  claim 1 , wherein the effective amount comprises about 0.1 mg/day to about 500 mg/day of dextromethorphan. 
     
     
         3 . The method of  claim 1 , wherein the pharmaceutical composition is administered by intravenous infusion, by transdermal delivery, or orally as a tablet or a capsule. 
     
     
         4 . The method of  claim 1 , further comprising administering to the subject a CYP2D6 inhibitor that is effective to prolong the half life of dextromethorphan in the subject. 
     
     
         5 . A pharmaceutical composition for treating hypertension or a symptom associated therewith in a subject, comprising an effective amount of dextromethorphan, an effective amount of a calcium channel blocker, and a pharmaceutically acceptable carrier. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the calcium channel blocker is selected from the group consisting of amlodipine, bepridil, clentiazem, diltiazem, fendiline, gallopamil, mibefradil, prenylamine, semotiadil, terodiline, verapamil, aranidipine, barnidipine, benidipine, cilnidipine, efonidipine, elgodipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, cinnarizine, flunarizine, lidoflazine, lomerizine, bencyclane, etafenone, perhexyline and fluspirilene. 
     
     
         7 . The pharmaceutical composition of  claim 5 , comprising about 0.1 mg to about 500 mg of dextromethorphan and about 0.01 mg to about 100 mg of the calcium channel blocker per dosage form. 
     
     
         8 . The pharmaceutical composition of  claim 5 , comprising about 1 mg to about 300 mg of dextromethorphan and about 0.5 mg to about 20 mg of the calcium channel blocker per dosage form. 
     
     
         9 . A method of treating hypertension or a symptom associated therewith in a subject, comprising administering to the subject an effective amount of dextromethorphan and an effective amount of a calcium channel blocker. 
     
     
         10 . The method of  claim 9 , wherein the dextromethorphan and the calcium channel blocker are administered in a pharmaceutical composition comprising the effective amount of dextromethorphan, the effective amount of a calcium channel blocker, and a pharmaceutically acceptable carrier. 
     
     
         11 . The method of  claim 9 , further comprising administering to the subject a CYP2D6 inhibitor that is effective to prolong the half life of dextromethorphan in the subject. 
     
     
         12 . The method of  claim 9 , wherein the calcium channel blocker and dextromethorphan are administered in a dosage ratio of calcium channel blocker: dextromethorphan as 1:0.5 to 1:100. 
     
     
         13 . A pharmaceutical composition for treating hypertension or a symptom associated therewith in a subject, comprising an effective amount of dextromethorphan, an effective amount of amlodipine, and a pharmaceutically acceptable carrier. 
     
     
         14 . The pharmaceutical composition of  claim 13 , comprising about 0.1 mg to about 500 mg of dextromethorphan and about 0.01 mg to about 100 mg of amlodipine per dosage form. 
     
     
         15 . The pharmaceutical composition of  claim 13 , comprising about 10 mg to about 100 mg of dextromethorphan and about 0.5 mg to about 20 mg of amlodipine per dosage form. 
     
     
         16 . The pharmaceutical composition of  claim 13 , wherein the amlodipine is a substantially optically pure S-(−)-amlodipine. 
     
     
         17 . The pharmaceutical composition of  claim 13 , wherein the amlodipine is (R,S)-amlodipine. 
     
     
         18 . The pharmaceutical composition of  claim 13 , comprising a ratio of amlodipine: dextromethorphan of 1:0.5 to 1:100. 
     
     
         19 . A method of treating hypertension or a symptom associated therewith in a subject, comprising administering to the subject an effective amount of dextromethorphan and an effective amount of amlodipine. 
     
     
         20 . The method of  claim 19 , wherein the dextromethorphan and the amlodipine are administered in a pharmaceutical composition comprising the effective amount of dextromethorphan, the effective amount of amlodipine, and a pharmaceutically acceptable carrier. 
     
     
         21 . The method of  claim 19 , further comprising administering to the subject a CYP2D6 inhibitor that is effective to prolong the half life of dextromethorphan in the subject. 
     
     
         22 . A pharmaceutical composition for treating hypertension or a symptom associated therewith in a subject, the pharmaceutical composition comprising an effective amount of a calcium channel blocker, an effective amount of a NADPH oxidase inhibitor, and a pharmaceutically acceptable carrier. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein the calcium channel blocker is selected from the group consisting of amlodipine, bepridil, clentiazem, diltiazem, fendiline, gallopamil, mibefradil, prenylamine, semotiadil, terodiline, verapamil, aranidipine, barnidipine, benidipine, cilnidipine, efonidipine, elgodipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, cinnarizine, flunarizine, lidoflazine, lomerizine, bencyclane, etafenone, perhexyline and fluspirilene; and wherein the NADPH oxidase inhibitor is selected from the group consisting of gp91ds-tat, apocynin, diphenylene iodonium, aminoethyl benzenesulfono fluoride, S17834, PR39, protein kinase C inhibitors, VAS2870, angiotensinconverting enyzme inhibitors, angiotensin receptor blockers, statins, and dextromethorphan. 
     
     
         24 . A method of treating hypertension or a symptom associated therewith in a subject, comprising administering to the subject an effective amount of a calcium channel blocker and an effective amount of a NADPH oxidase inhibitor. 
     
     
         25 . The method of  claim 24 , wherein the calcium channel blocker and the NADPH oxidase inhibitor are administered in a pharmaceutical composition comprising the effective amount of the calcium channel blocker, the effective amount of the NADPH oxidase inhibitor, and a pharmaceutically acceptable carrier.