Treatment of Angina

Nitroglycerin remains the dmg of choice for treatment of angina pectoris. It has also been found useful for the treatment of congestive heart failure, myocardial infarction, peripheral vascular disease, such as Raynaud s disease, and mitral insufficiency, although the benefits of nitroglycerin in mitral insufficiency have been questioned. 

Nitroglycerin Delivery Systems. Transderm-Nitro, Nitro-dur, and Minitran are all transdermal therapeutic systems that dehver nitroglycerin [55-63-0] mol wt 227.09, at a continuous, controlled rate through intact skin for treatment of angina (95). 

Substitution of additional basic groups onto a closely related nucleus affords a compound with muscle relaxant activity with some activity in the treatment of angina. Reaction of the... 

Prenyl amine (66) was long used in the treatment of angina pectoris, in which condition it was believed to act by inhibiting the uptake and storage of catecholamines in heart tissue. Droprenilamine (69), an analogue in which the phenyl ring is reduced, acts as a coronary vasodilator. One of several syntheses involves simple reductive alkylation of 1,1-diphenyl-propylamine (67) with cyclohexyl acetone (68)... 

The so-called calcium channel blockers constitute a class of cardiovascular agents that have gained prominence in the past few years. These drugs, which obtund contraction of arterial vessels by preventing the movement of calcium ions needed for those contractions, have proved especially useful in the treatment of angina and hypertension. Dihydropyridines such as nifedipine (30) are par-... 

A number of diarylmethyl alkylpiperazines, such as, for example lidoflazine, have found use as coronary vasodilators for the treatment of angina. The most recent of these interestingly incorporates a 2,6-dichloroaniline moiety reminiscent of antiarrhythmic agents. Treatment of the piperazine carboxamide 124 with acetone leads to formation of the nitrogen analogue of an acetal, the aminal 125. Alkylation of the remaining secondary nitrogen with chloroamide 126 leads to the intermediate 127. Exposure to aqueous acid leads to hydrolysis of the aminal function... 

DHPs are potent arterial vasodilators. They act on resistance vessels and therefore reduce peripheral vascular resistance, lower arterial blood pressure, and antagonize vasospasms in coronary or peripheral arteries. By reducing afterload, DHPs also reduce cardiac oxygen demand. Together with their vascular spasmolytic effect, this explains most of the beneficial actions of DHPs in angina pectoris. Most DHPs are only licensed for the therapy of hypertension, some of them also for the treatment of angina pectoris and vasospastic (Prinzmetal) angina. 

Dobutamine (76), on the other hand, is a dopamine derivative which does not act centrally, but is of interest because of its coronary vasodilator properties. Such drugs are potentially of value in treatment of angina pectoralis. Further, it is now undergoing extensive clinical trials as an inotropic agent for use in heart failure. Its synthesis is effected by Raney nickel catalyzed reduction of methyl p-methoxyvinylphenylketone (75) to its dihydro analog followed by reductive alkylation with p-(3,4-dimethoxyphenyl)ethylamine. The ether groups are cleaved with HBr to complete the synthesis of... 

Katzung, B.G. and Chatterjee, K., Vasodilators and the treatment of angina pectoris, in Basic and Clinical Pharmacology, 8th ed., Katzung, B.G., Ed., Lange Medical Books/McGraw-Hill, New York, 2001, chap. 12. 

S -nitrosothiols, several of which occur naturally, e.g., iS -nitrosocysteine and S-nitrosoglutathione, have an important role in NO transport and regulation in biological systems. Potential applications of RSNO compounds include their use as vasodilators in the treatment of angina and in the search for a cure for male impotence.11 The most convenient route to S-nitrosothiol formation is the nitrosation of thiols. 

Ivabradine is used in the treatment of angina in patients in normal sinus rhythm. It acts on the sinus node resulting in a reduction of the heart rate. It is contraindicated in severe bradycardia (heart rate lower than 60 beats/ minute), cardiogenic shock, acute myocardial infarction, moderate-to-severe heart failure, immediately after a cerebrovascular accident, second and third-degree heart block and patients with unstable angina or a pacemaker. Side-effects include bradycardia, first-degree heart block, ventricular extrasystoles, headache, dizziness and visual disturbances, including blurred vision. 

The drug nitroglycerin (glyceryl trinitrate), which is used in the treatment of angina pectoris, releases NO in the bloodstream and thereby leads to better perfusion of cardiac muscle. 

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