Treatment of cardiovascular and related pathologies
View Patent ↗Methods for treating cardiovascular and related diseases such as ischemia, ischemia reperfusion injuries, and myocardial ischemia, are described. The methods are directed to concurrently administering a compound such as pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, or a 3-acylated pyridoxal analogue with a therapeutic cardiovascular compound.
1. A method of treating ischemia reperfusion injury in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount for treating ischemia reperfusion injury of a combination of a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxal, pyridoxamine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof, and a therapeutic cardiovascular compound selected from the group consisting of an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a calcium channel blocker, a β-adrenergic receptor antagonist, a vasodilator, a diuretic, an α-adrenergic receptor antagonist, an antioxidant, and a mixture thereof,
wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; and
R 2 is a secondary amino group.
2. A method according to claim 1 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group.
3. A method according to claim 1 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; and
R 2 is a secondary amino group.
4. A method according to claim 1 , wherein the angiotensin converting enzyme inhibitor is captopril, enalapril, lisinopril, benazapril, fosinopril, quinapril, ramipril, spirapril, imidapril, or moexipril.
5. A method according to claim 1 , wherein the angiotensin II receptor antagonist is losartan or valsartan.
6. A method according to claim 1 , wherein the calcium channel blocker is verapamil, diltiazem, nicardipine, nifedipine, amlodipine, felodipine, nimodipine, or bepridil.
7. A method according to claim 1 , wherein the compound is administered enterally or parenterally and the therapeutic cardiovascular compound is administered enterally or parenterally.
8. A method according to claim 1 , wherein the compound and the therapeutic cardiovascular compound are administered in a single dosage form.
9. A method according claim 1 , wherein the vasodilator is hydralazine, nitroglycerin, or isosorbide dinitrate.
10. A method according to claim 1 , wherein the α-adrenergic receptor antagonist is prazosin, doxazocin, or labetalol.
11. A method according to claims 1 , wherein the antioxidant is vitamin E, vitamin C, or an isoflavone.
12. A method according to claim 1 , wherein the diuretic is furosemide, diuril, amiloride, or hydrodiuril.
13. A method according to claim 1 , wherein the α-adrenergic receptor antagonist is atenolol, propranolol, timolol, or metoprolol.