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Antinociceptive effects of the alkaloid epibatidine: Further studies on involvement of nicotinic receptors
Author(s) -
Badio Barbara,
Shi Dan,
Martin H. Martin,
Daly John W.
Publication year - 1995
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430360108
Subject(s) - epibatidine , nicotine , nicotinic agonist , pharmacology , cytisine , chemistry , methyllycaconitine , nicotinic antagonist , alkaloid , acetylcholine receptor , receptor , nicotinic acetylcholine receptor , biology , biochemistry , stereochemistry , neuroscience
Epibatidine is a potent analgetic agent with high affinity for nicotinic receptors. The antinociceptive effects of epibatidine are blocked by both competitive and noncompetitive nicotinic antagonists. The L‐type calcium channel activator Bay K 8644 potentiates the antinociceptive effects of epibatidine, while nifedipine antagonizes the antinociceptive effects. Acute treatment with chlorisondamine leads to long‐term blockade of the antinociceptive effects of epibatidine. The antinociceptive effects of epibatidine are reduced in mice rendered tolerant to the behavioral effects of nicotine by chronic nicotine or caffeine treatment. Epibatidine has very high affinity for the major central nicotinic receptor to which [ 3 H]nicotine binds. However, unlike nicotine and cytisine, epibatidine is very potent at ganglionic‐type nicotinic receptors. Epibatidine in cultured cells causes desensitization of both ganglionic and neuromuscular nicotinic receptors. Thus, like nicotine, chronic treatment with epibatidine might be expected to lead to tolerance. These studies establish epibatidine as a tool for the study of nicotinic pathways involved in pain perception. © 1995 Wiley‐Liss, Inc.