title: Isradipine decreases the hemodynamic response of cocaine and methamphetamine results from two human laboratory studies: results from two human laboratory studies.
abstract: 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.
authors.affiliation: Department of Psychiatric Medicine, University of Virginia, Charlottesville, Virginia 22908-0623, USA. bnkolejohnson@virginia.edu
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: Lynda T
authors.initials: LT
authors.lastname: Wells
authors.forename: John D
authors.initials: JD
authors.lastname: Roache
authors.forename: Christopher
authors.initials: C
authors.lastname: Wallace
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000150:complications; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000150:complications; D018592:Cross-Over Studies; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D007275:Injections, Intravenous; D017275:Isradipine / Q000627:therapeutic use*; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control
chemical_list: D002121:Calcium Channel Blockers; D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; D003042:Cocaine; D017275:Isradipine