Mechanisms involved in the respiratory depressant actions of nicotine in anesthetized rats.
In the urethane-pentobarbital anesthetized rat, the respiratory depressant and lethal effects of intravenously infused (-)-nicotine (120 micrograms/kg/min) or (+)-nicotine (600 micrograms/kg/min) were effectively prevented by pretreatment with the opioid antagonist, naltrexone, whereas the lethal effect of (-)-nicotine (120 micrograms/kg/min) was not altered by bilateral adrenalectomy. Further, pretreatment with either the nicotinic ganglion-blocker, mecamylamine, a secondary amine, or the quarternary nicotinic ganglion-blocker, hexamethonium, completely prevented the lethal effects of (-)-nicotine (120 micrograms/kg/min). These data suggest that central opioidergic and nicotinic processes are involved in nicotine's respiratory depressant and lethal effects.
Sloan
J W
JW
Department of Pharmacology, University of Kentucky, Lexington 40536.
Martin
W R
WR
Bostwick
M
M
D000758:Anesthesia; D000818:Animals; D005260:Female; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology* / Q000633:toxicity; D010424:Pentobarbital; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects*; D014520:Urethane
D006584:Hexamethonium Compounds; D011978:Receptors, Nicotinic; D011957:Receptors, Opioid; D018738:Hexamethonium; D014520:Urethane; D009271:Naltrexone; D008464:Mecamylamine; D009538:Nicotine; D010424:Pentobarbital