Antagonism of ethanol intoxication in rats by inhibitors of phenylethanolamine N-methyltransferase.
The probable involvement of brain epinephrine in the expression of the acute sedative and intoxicating effects of ethanol and pentobarbital is demonstrated. Two selective inhibitors of phenylethanolamine N-methyltransferase (PNMT), LY134046 and LY78335, proved to be potent and long-lasting antagonists of ethanol intoxication in rats. Acute antagonism of pentobarbital-induced intoxication was observed with LY134046. The present results are compatible with a role for central epinephrine synthesis in ethanol and pentobarbital-induced sedation and intoxication in rats.
Mefford
I N
IN
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892.
Lister
R G
RG
Ota
M
M
Linnoila
M
M
D000435:Alcoholic Intoxication / Q000517:prevention & control*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D003975:Diazepam / Q000037:antagonists & inhibitors; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010424:Pentobarbital / Q000037:antagonists & inhibitors; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D044005:Tetrahydroisoquinolines
D001552:Benzazepines; D001596:Benzylamines; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C002569:2,3-dichloro-alpha-methylbenzylamine; C028625:LY 134046; C012153:7,8-dichloro-1,2,3,4-tetrahydroisoquinoline; D010625:Phenylethanolamine N-Methyltransferase; D010424:Pentobarbital; D003975:Diazepam