title: Pharmacological effects of epibatidine optical enantiomers.
abstract: The pharmacology of synthetic D- and L-epibatidine, an alkaloid originally characterized from frog skin, were studied in different behavioral tests in mice and rats. The two enantiomers have potent antinociceptive activity in mice using the tail-flick test, with an ED50 of 6.1 and 6.6 micrograms/kg for L- and D-epibatidine respectively. Epibatidine enantiomers were 200 x more potent than L-nicotine as an antinociceptive agent in mice after s.c. administration. Their analgesic effect was blocked by mecamylamine but not naloxone, an opiate antagonist. Both D- and L-epibatidine have high affinity (Ki 54.7 and 55.0 pM, respectively) for [3H]nicotine binding site in rat brain. In addition, they reduced mice locomotor activity and body temperature in a dose-dependent manner. In rats trained with nicotine (0.4 mg/kg), epibatidine enantiomers engendered nicotine-like responding in a dose-related manner with an ED50 of 1.00 and 0.93 micrograms/kg for D and L, respectively. The discriminative effect of L- and D-epibatidine in rats was blocked by mecamylamine but not by hexamethonium. As in binding results, there was no significant enantioselectivity for these effects in our study.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
authors.forename: M I
authors.initials: MI
authors.lastname: Damaj
authors.forename: K R
authors.initials: KR
authors.lastname: Creasy
authors.forename: A D
authors.initials: AD
authors.lastname: Grove
authors.forename: J A
authors.initials: JA
authors.lastname: Rosecrans
authors.forename: B R
authors.initials: BR
authors.lastname: Martin
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004193:Discrimination Learning; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D010147:Pain Measurement; D011725:Pyridines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D012055:Reinforcement Schedule; D013237:Stereoisomerism
chemical_list: D000700:Analgesics; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; C082748:epibatidine