Isradipine decreases the hemodynamic response of cocaine and methamphetamine: Results from two human laboratory studies

Background: Massive hypertensive crises relating to cerebrovascular accidents such as strokes or ruptured aneurysms, or cardiovascular dysfunction and toxicity, are an important cause of morbidity and mortality associated with cocaine or methamphetamine use. Experimentally administered, pharmacologically effective doses of cocaine and methamphetamine may serve as a model for studying the effects of these drugs on hemodynamic response and for examining the potential utility of the antihypertensive and dihydropyridine-class calcium channel antagonist isradipine to block these effects. We therefore examined, in two separate experiments of similar design conducted contemporaneously, the hemodynamic effects of cocaine or methamphetamine in the presence and absence of isradipine. Methods: In both experiments (total N = 31), isradipine pretreatment was provided to cocaine- or methamphetamine-dependent male and female subjects before intravenous administration of low and high doses of cocaine (0.325 or 0.650 mg/kg) or methamphetamine (15 or 30 mg), respectively, on separate test days. Results: Both cocaine and methamphetamine administration produced predicted elevations in blood pressure (with peak response between 1 and 3 min after infusion). Apart from tachycardia, no arrhythmias were reported. Isradipine significantly reduced stimulant-associated increases in all measures of blood pressure except pulse pressure, but tended to enhance the effects of these drugs on heart rate. Conclusions: Clinical studies are needed to determine whether isradipine is therapeutically efficacious in preventing hypertensive crises and the associated cerebrovascular and cardiovascular sequelae in cocaine- or methamphetamine-dependent individuals. As there is no established pharmacotherapy for treating cocaine or methamphetamine dependence, identification of a medication that reduces the harmful medical consequences of these drugs would be scientifically and clinically important.