In vivo enantioselectivity of epibatidine interaction with calcium-modulating drugs.
Several recent studies have implicated the involvement of calcium ion fluxes in the response to nicotine on a cellular level. The influence of a calcium agonist (BAY K 8644) and calcium blockers on (+)- and (-)-epibatidine-induced antinociception was investigated in mice using the tail-flick test. The effect of (+)-epibatidine but not (-)-epibatidine was significantly increased by BAY K 8644 pretreatment. This potentiation by BAY K 8644 was blocked by pretreating the animals with nifedipine at 2 mg/kg. The calcium channel antagonist, nimodipine, reduced significantly the antinociception induced by (+)-epibatidine but not (-)-epibatidine (12 microg/kg, s.c.). Similar results were also observed with the calcium chelator EGTA. Thus, epibatidine isomers pharmacological effect was differentially modulated by calcium signaling process secondary to receptor activation.
Imad Damaj
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Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Box 980613, Richmond, VA 23298-0613, USA. mdamaj@hsc.vcu.edu
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D011725:Pyridines; C082748:epibatidine; D002118:Calcium