piperidines and Angina-Pectoris--Variant

This study was designed to test the hypothesis of a possible role of serotonin in the pathogenesis of myocardial ischemia in patients with pure vasospastic angina, since serotonin is known to cause contraction in isolated coronary arteries. This effect, as well as serotonin-induced platelet aggregation, is reversed by ketanserin, a specific S2-receptor blocker. Five male patients (49 to 68 years old) with more than six episodes/day of myocardial ischemia at rest as characterized by ST segment elevation on the electrocardiogram (ECG) were selected for the study after a 2 day run-in period of continuous ECG Holter monitoring in the absence of any therapy except that with sublingual nitrates. In a double-blind crossover protocol they received consecutive infusions of 6 hr each of ketanserin (2 mg/hr iv, preceded by a 10 mg bolus in three patients) and placebo in the following sequence: ketanserin-placebo-ketanserin-placebo in the first and placebo-ketanserin-placebo-ketanserin in the second 24 hr period. The efficacy of the infused drug was tested by exposing platelet-rich plasma, obtained from the study patients at a fixed morning time before and during ketanserin infusions, to a series of serotonin concentrations from 10(-5) to 10(-8)M in a conventional aggregometer. A complete suppression of aggregation curves in the range of serotonin concentrations tested resulted during administration of ketanserin. The efficacy of the drug in preventing ischemic episodes was assessed by computing the ischemic episodes (recorded by Holter monitoring) and nitroglycerin consumption in each 6 hr ketanserin period and in the corresponding placebo period. A total of 171 ischemic episodes were recorded, 33 of which (19%) were symptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Angina Pectoris, Variant; Coronary Disease; Coronary Vasospasm; Double-Blind Method; Drug Evaluation; Hemodynamics; Humans; Ketanserin; Male; Middle Aged; Piperidines; Placebos; Platelet Aggregation; Serotonin; Serotonin Antagonists

Three patients with variant angina pectoris resistant to therapy with nitrates and propranolol were treated with perhexilene maleate. Two patients had normal coronary arteries with documented coronary artery spasm, while the third patient had a fixed coronary artery obstruction. In all three patients, attacks of variant angina pectoris disappeared following institution of therapy with perhexilene maleate. When the dose of this drug was decreased to 100 mg per day or less, symptoms reappeared in all patients. Reinstitution of therapeutic doses of perhexilene maleate once again resulted in complete control of symptoms. Perhexilene maleate is therefore a useful agent for the treatment of variant angina pectoris.

Topics: Angina Pectoris; Angina Pectoris, Variant; Coronary Angiography; Drug Evaluation; Electrocardiography; Female; Humans; Male; Middle Aged; Nitroglycerin; Perhexiline; Piperidines

Topics: Adult; Aged; Angina Pectoris; Angina Pectoris, Variant; Electrocardiography; Ergonovine; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Nifedipine; Perhexiline; Piperidines; Pyridines