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.