Adrenoceptor mechanisms in the cardiovascular effects of cocaine in conscious squirrel monkeys.
The purpose of the current experiment was to study the role of various adrenoceptor subtypes in the cardiovascular response to cocaine in conscious squirrel monkeys. A variety of adrenoceptor antagonists were administered i.v. prior to the administration of 0.3 mg/kg cocaine (i.v.). Cocaine alone produced an increase in both blood pressure and heart rate. The non-selective alpha adrenoceptor antagonist phentolamine produced a dose-dependent antagonism of the pressor effect of cocaine, as did the alpha-1 selective antagonist prazosin. The alpha-2 selective antagonist yohimbine had no effect on the pressor effect of cocaine. The non-selective beta antagonist propranolol enhanced the pressor effect of cocaine as did the beta-1 selective antagonist atenolol. However, the effect of atenolol was not dose-dependent. The beta-2 selective antagonist ICI 118,551 and labetalol, which blocks both alpha and beta adrenoceptors, did not alter the pressor effect of cocaine. Propranolol, atenolol, and labetalol all antagonized the tachycardiac effect of cocaine in a dose-dependent manner, while the beta-2 antagonist ICI 118,551 did not. Phentolamine, prazosin and yohimbine also reduced the tachycardiac effect of cocaine, although these effects were dose-dependent only for yohimbine, which also significantly elevated baseline heart rate. These results indicate that alpha-1 adrenoceptor mechanisms mediate the pressor effect of cocaine, while beta-1 adrenoceptor mechanisms are involved in the tachycardiac effect of cocaine in squirrel monkeys. Propranolol potentiated cocaine's pressor effect through beta-2 independent mechanisms. Thus, neither alpha-2 nor beta-2 adrenoceptor mechanisms appear to be involved in cocaine's cardiovascular effects.
Behavioral Pharmacology and Genetics Laboratory, NIDA Addiction Research Center, Baltimore, MD 21224.
C W
CW
Schindler
S R
SR
Tella
S R
SR
Goldberg
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007741:Labetalol / Q000494:pharmacology; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012453:Saimiri; D015016:Yohimbine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; C026777:ICI 118551; D001262:Atenolol; D011433:Propranolol; D003042:Cocaine; D007741:Labetalol; D011224:Prazosin; D010646:Phentolamine