PHARMACOLOGICAL EFFECTS OF EPIBATIDINE OPTICAL ENANTIOMERS

The pharmacology of synthetic D- and L-epibatidine, an alkaloid origin ally characterized from frog skin, were studied in different behaviora l tests in mice and rats. The two enantiomers have potent antinocicept ive activity in mice using the tail-flick test, with an ED(50) of 6.1 and 6.6 mu g/kg for L- and D-epibatidine respectively. Epibatidine ena ntiomers were 200 X more potent than L-nicotine as an antinociceptive agent in mice after s.c. administration. Their analgesic effect was bl ocked by mecamylamine but not naloxone, an opiate antagonist. Both D- and L-epibatidine have high affinity (K-i 54.7 and 55.0 pM, respective ly) for [H-3]nicotine binding site in rat brain. In addition, they red uced mice locomotor activity and body temperature in a dose-dependent manner. In rats trained with nicotine (0.4 mg/kg), epibatidine enantio mers engendered nicotine-like responding in a dose-related manner with an ED(50) of 1.00 and 0.93 mu g/kg for D and L, respectively. The dis criminative effect of L- and D-epibatidine in rats was blocked by meca mylamine but not by hexamethonium. As in binding results, there was no significant enantioselectivity for these effects in our study.