The effects of two different inhibitors of PNMT and their interactions with ethanol.
The effects of two structurally different inhibitors of phenylethanolamine-N-methyltransferase, LY 134046 and CGS 19281A were investigated in a holeboard test of directed exploration and locomotor activity. Both compounds dose-dependently reduced exploratory head-dipping without affecting locomotor activity. The interaction of each drug with ethanol was also studied by testing the ataxia. Administration of these compounds had differential effects in a test of ethanol-induced ataxia. LY 134046 significantly attenuated ethanol-induced ataxia whereas CGS 19281A was without effect or (at 50 mg kg-1) potentiated ethanol's effect. These results suggest that the ethanol attenuating properties of LY 134046 may not solely be due the inhibition of PNMT and that its alpha 2-adrenoceptor blocking properties may be playing a role.
Durcan
M J
MJ
Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Lister
R G
RG
Linnoila
M
M
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D012016:Reference Values
D001552:Benzazepines; D002243:Carbolines; C062736:4,9-dihydro-7-methoxy-3H-pyrido(3,4b)indole; D000431:Ethanol; C028625:LY 134046; D010625:Phenylethanolamine N-Methyltransferase