Sympathetic nervous system mediated cardiovascular effects of cocaine are primarily due to a peripheral site of action of the drug.
Currently, augmentation of sympathetic nervous system function produced by cocaine is thought to be due primarily to stimulation of sympathetic centers in the brain (central effect) and to inhibition of catecholamine uptake into postganglionic sympathetic nerve terminals (peripheral effect). In this review of our work, we present the following evidence that cocaine-induced changes in cardiovascular function, particularly those that peak within 1 to 5 min after an i.v. bolus injection of the drug, are due to a peripheral effect of the drug: (1) In both dogs and cats, cocaine potentiates the tachycardiac effect of neurally-released and injected norepinephrine (NE). The time course of action and dosage range of cocaine that produces potentiation follows that which increases blood pressure (BP), heart rate (HR), rate-pressure product and coronary vasoconstriction. (2) Cocaine given in i.v. doses that increase BP in decerebrate cats (0.25-1.0 mg/kg) has no significant effect on directly monitored spontaneous cardiac sympathetic nerve activity (SNA). In fact, higher doses of cocaine (2-4 mg/kg, i.v.) consistently inhibit preganglionic cardiac and splanchnic nerve activity. (3) Cocaine (0.1-1.0 mg) administered directly into the blood supply of the hindbrain via the vertebral artery produces no increase in BP, HR or SNA in cats; instead, decreases in BP and sympathetic activity occur. The same dose (1 mg), injected i.v., does not depress BP or SNA. In addition, cocaine injected into the forebrain via the carotid artery or into the cerebral ventricles (0.1-1.0 mg) has very little effect on BP. Our results indicate that there is no significant excitatory effect of cocaine on CNS sympathetic centers, and that the sympathomimetic effects of cocaine on the cardiovascular system are likely to be mediated at peripheral sites.
Gillis
R A
RA
Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007, USA.
Hernandez
Y M
YM
Erzouki
H K
HK
Raczkowski
V F
VF
Mandal
A K
AK
Kuhn
F E
FE
Dretchen
K L
KL
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002319:Cardiovascular System / Q000294:innervation*; D002415:Cats; D003042:Cocaine / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D009638:Norepinephrine / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D003042:Cocaine; D009638:Norepinephrine