Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys.
As kappa agonists have been proposed as treatments for cocaine abuse, the cardiovascular effects of the kappa opioid receptor agonists ethylketocyclazocine (EKC) and enadoline were investigated in conscious squirrel monkeys. Both EKC and enadoline increased heart rate with little effect on blood pressure. This effect appeared to be specific for kappa receptors as the mu opioid agonist morphine did not mimic the effects of the kappa agonists. The opioid antagonist naltrexone, at a dose of 1.0 mg/kg, blocked the effect of EKC. An action at both central and peripheral receptors may be responsible for the heart rate increase following kappa agonist treatment. The ganglionic blocker chlorisondamine partially antagonized the effect of EKC on heart rate, suggesting central involvement, while the peripherally-acting agonist ICI 204,448 ((+/-)-1-[2,3- (Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) also increased heart rate, supporting a peripheral site of action. When given in combination with cocaine, EKC produced effects that were sub-additive, suggesting that the kappa agonists may be used safely as cocaine abuse treatments.
Schindler
Charles W
CW
Preclinical Pharmacology Section, Behavioral Neuroscience Branch, DHHS/NIH/NIDA Intramural Research Program, Baltimore MD (CWS, ZG, JPG, SRG), United States. cschindl@helix.nih.gov
Graczyk
Zofi
Z
Gilman
Joanne P
JP
Negus
S Stevens
SS
Bergman
Jack
J
Mello
Nancy K
NK
Goldberg
Steven R
SR
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000503:physiopathology; D004347:Drug Interactions; D016314:Ethylketocyclazocine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D012453:Saimiri
D001572:Benzofurans; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D016314:Ethylketocyclazocine; D003042:Cocaine; C067110:enadoline
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