Drugs selective for nicotinic receptor subtypes: a real possibility or a dream?

Nicotine exerts a number of different effects on the nervous system by inte racting with neuronal nicotinic acetylcholine receptors (nAChRs). These eff ects are mediated by its interaction with different nAChR subtypes, and thi s has led to the finding of subtype specific agonists and antagonists. In t he search for subtype-selective drugs, we have synthesized some compounds d erived from 4-oxystilbene, two of which (MG624 and F3) are selective ligand s for the chick neuronal alpha Bgtx receptors containing the alpha 7 and /o r alpha 8 subunits. They have an antagonist action on oocyte-expressed chic k and rat alpha 7 subtypes. These compounds are selective toward the alpha 7-containing receptors in chick, but, in mammals, although they still retai n their potency toward alpha 7-containing receptors, they are also active i n non-alpha 7-containing receptors. (C) 2000 Elsevier Science B.V. All righ ts reserved.