Ethylketocyclazocine decreases noradrenaline release and blood pressure in the rabbit at a peripheral opioid receptor.
Rabbits were pithed and their sympathetic outflow was stimulated electrically via the pithing rod. Arterial blood pressure, heart rate, the endogenous plasma noradrenaline level, the plasma 3H-noradrenaline clearance and the noradrenaline release rate (the rate of entry of endogenous noradrenaline into the plasma) were determined. Ethylketocyclazocine 0.1 mg kg-1 + 0.02 mg kg-1 h-1 and 1 mg kg-1 + 0.2 mg kg-1 h-1 but not 0.01 mg kg-1 + 0.002 mg kg-1 h-1 decreased blood pressure, the endogenous plasma noradrenaline level and the noradrenaline release rate. The effects of ethylketocyclazocine 1 mg kg-1 + 0.2 mg kg-1 h-1 were antagonized by naloxone 1 mg kg-1 + 0.5 mg kg-1 h-1. Given alone, naloxone caused no change. It is concluded that ethylketocyclazocine inhibits action potential-evoked release of noradrenaline from postganglionic sympathetic neurones, and hence can lower blood pressure, by a peripheral effect, possibly mediated by opioid receptors at the terminal axons.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003655:Decerebrate State; D004558:Electric Stimulation; D016314:Ethylketocyclazocine; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects*
D011957:Receptors, Opioid; D009270:Naloxone; D016314:Ethylketocyclazocine; D003496:Cyclazocine; D009638:Norepinephrine