The effects of cocaine and other psychomotor stimulants on a number of physiological parameters are being studied. Recent studies in squirrel monkeys have indicated that alpha-1 adrenergic mechanisms are importantly involved in the pressor effects of both cocaine and methamphetamine, while beta-1 adrenergic mechanisms are important for the tachycardiac effect of both drugs. Unlike with cocaine, dopaminergic mechanisms are involved in the cardiovascular effects of methamphetamine. The cardiovascular effects of cocaine in rats are completely antagonized by noncompetitive or mixed type autonomic ganglionic blockers, while only partially antagonized by the competitive ganglionic blockers. Thus, these results provide substantial evidence that the cardiovascular effects of cocaine in conscious rats are mainly centrally medicated. Acute lethality studies indicate that various adrenergic agents modify acute cocaine intoxication. These studies also indicated that convulsant activity, rather than either cardiovascular or respiratory failure, is primarily responsible for the acute lethal effects of cocaine in conscious animals. Additional studies clearly demonstrate that central stimulation of sympathoadrenal neural axis plays an important role in cocaine's cardiovascular effects. Further, the pressor effect of cocaine is mainly medicated by catecholamines of sympathetic neural origin, whereas the tachycardiac effect is mainly mediated by catecholamines of adrenal medullary origin. We have also recently begun investigations of the effects of the major cocaine metabolites in anesthetized rats. Like cocaine, the cocaine metabolites norcocaine and cocaethylene (a metabolite produced during co-administration of cocaine and ethanol) have potent local anesthetic effects. Benzoylecgonine, ecgonine methyl ester and ecgonine did not produce local anesthetic effects. Benzolyecgonine and ecgonine methyl ester did possess potent sympathomimetic effects however. These potent sympathomimetic effects in the absence of a counteracting local anesthetic effect may account for some of the toxicity observed hours following cocaine administration.
