Pharmacological mechanisms in cocaine's cardiovascular effects.
The squirrel monkey is a reliable model for the cardiovascular effects of cocaine in that it mimics the human response to cocaine; low to moderate doses of cocaine produce a sustained pressor effect and tachycardia. Pretreatment experiments have indicated the importance of alpha-1 and beta-1 adrenoceptor mechanisms in mediating the pressor and tachycardiac effects of cocaine, respectively. Little support for a role of dopaminergic mechanisms in the hemodynamic effects of cocaine has been found. Toxicity to cocaine is often observed hours after its administration, pointing to a potential role of the cocaine metabolites. Studies on the direct effects of a variety of cocaine metabolites indicate that their cardiovascular effects do not necessarily mimic those produced by cocaine, and therefore these differing effects of the metabolites should be considered when evaluating the cardiovascular toxicity of cocaine. Further, as these metabolites are present in the body for long periods of time, these results suggest a role of the metabolites in producing toxicity long after cocaine administration. Finally, studies using both dopaminergic and calcium channel antagonists indicate that the pharmacological mechanisms involved in the cardiovascular effects of cocaine are not the same as those involved in its behavioral effects.
Schindler
C W
CW
Behavioral Pharmacology and Genetics Section, NIH/NIDA Division of Intramural Research, Baltimore, MD 21122, USA.
Tella
S R
SR
Erzouki
H K
HK
Goldberg
S R
SR
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000294:innervation; D003042:Cocaine / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects; D012453:Saimiri
D015220:Calcium Channels; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D003042:Cocaine