The α7 nicotinic acetylcholine receptor (α7 nAChR) is a potential therapeutic target for the treatment of cognitive deficits associated with schizophrenia, Alzheimer's disease, Parkinson's disease, and attention deficit hyperactivity disorder. Dinklo et al. describe the pharmacological profile of a highly selective α7 nAChR positive allosteric modulator (PAM) 2-[[4-fluoro-3-(trifluoromethyl)phenyl]amino]-4-(4-pyridinyl)-5-thiazolemethanol (JNJ-1930942). This compound is highly selective for the α7 nAChR in that it does not act on α4β2, α3β4 nAChRs or on the related 5-HT3A channel. JNJ-1930942 enhances the efficacy as well as the potency of an orthosteric agonist without activating the receptor on its own. The potentiation of nicotinic agonists by JNJ-1930942 is obtained mainly by affecting the receptor desensitization characteristics. The profile of JNJ-1930942 appears different from that of the type I and II PAMs described so far, suggesting that intermediate PAM types exist. In hippocampal slices, JNJ-1930942 increases synaptic transmission and facilitates long-term potentiation induction, suggesting a potential benefit to cognitive processes. These studies suggest that JNJ-1930942 could be a useful tool to study the therapeutic potential of α7 nAChR potentiation in central nervous system disorders involving a deficit in α7 nAChR neurotransmission.
See article at J Pharmacol Exp Ther 2011, 336:560–574.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics