Drugs selective for nicotinic receptor subtypes: a real possibility or a dream?
Nicotine exerts a number of different effects on the nervous system by interacting with neuronal nicotinic acetylcholine receptors (nAChRs). These effects are mediated by its interaction with different nAChR subtypes, and this has led to the finding of subtype specific agonists and antagonists. In the search for subtype-selective drugs, we have synthesized some compounds derived from 4-oxystilbene, two of which (MG624 and F3) are selective ligands for the chick neuronal alphaBgtx receptors containing the alpha7 and/or alpha8 subunits. They have an antagonist action on oocyte-expressed chick and rat alpha7 subtypes. These compounds are selective toward the alpha7-containing receptors in chick, but, in mammals, although they still retain their potency toward alpha7-containing receptors, they are also active in non-alpha7-containing receptors.
Gotti
C
C
Department of Medical Pharmacology, CNR Cellular and Molecular Pharmacology Center, University of Milan, Italy.
Carbonnelle
E
E
Moretti
M
M
Zwart
R
R
Clementi
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002645:Chickens; D006801:Humans; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D018733:Nicotinic Antagonists; D000644:Quaternary Ammonium Compounds; D011978:Receptors, Nicotinic; D013267:Stilbenes; D064569:alpha7 Nicotinic Acetylcholine Receptor; C118602:triethyl-(beta-4-stilbenoxyethyl)ammonium