Effects of isradipine, a dihydropyridine-class calcium channel antagonist,on D-methamphetamine-induced cognitive and physiological changes in humans

D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarc tion. We examined the utility of isradipine, a dihydropyridine-class calciu m channel antagonist, in treating d-methamphetamine induced hypertension an d evaluated its effects on cognitive function, both of which are mediated b y dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse ra te) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentiall y beneficial therapeutic effect was offset by a significant reflex rise in pulse rate, D-methamphetamine also improved attention, accuracy of reasonin g ability, and performance on computerized cognitive function tasks. D-meth amphetamine's cognitive improving effects were not altered significantly by isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance, Isradipine does not appear to enhance cognitive function i n healthy humans. (C) 2000 American College of Neuropsychopharmacology.