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Epibatidine is a potent but nonselective nAChR agonist. Its biological effects appear to be mediated largely by alpha4beta2 nAChRs. Surprisingly, only a limited number of epibatidine analogues have been synthesized and evaluated in in vitro assays. Even fewer analogues have received in vivo pharmacological evaluation. In this paper, SAR studies directed toward epibatidine analogues will be reviewed. (C) 2004 Elsevier Ltd. All rights reserved