Pharmacological mechanisms in the cardiovascular effects of methamphetamine in conscious squirrel monkeys

Abstract

The effects of methamphetamine were studied on cardiovascular function in conscious squirrel monkeys. Methamphetamine (0.1-3.0 mg/kg, IV) produced a dose-dependent increase in blood pressure. Its effects on heart rate were more complex, with lower doses (0.1-0.3 mg/kg) producing increases in heart rate and higher doses (1.0-3.0 mg/kg) producing decreases. To determine the pharmacological mechanisms involved in methamphetamine's effects, a number of drugs were tested as pretreatments to an injection of 0.2 mg/kg methamphetamine. This dose produced the maximal heart rate increase. The alpha 1-antagonist prazosin completely antagonized the effects of methamphetamine on blood pressure, while the nonselective beta-antagonist propranolol and beta 1-selective antagonist atenolol completely antagonized the tachycardiac effect of methamphetamine. The dopaminergic antagonists SCH 23390 and haloperidol antagonized some of the cardiovascular effects of methamphetamine. These results indicate that the pressor and tachycardiac effects of methamphetamine are mediated via alpha 1- and beta 1-adrenoceptor mechanisms, respectively. Dopaminergic mechanisms are also involved in methamphetamine's cardiovascular effects.