1-[(1-Methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines as mGluR2 Positive Allosteric Modulators for the Treatment of Psychosis
Journal of Medicinal Chemistry – March 02, 2011
Source: OpenAlex
Summary
A promising new series of mGluR2 positive allosteric modulators has been developed, showing significant potential in addressing psychosis. In tests with 30 mice, a lead compound, (+)-17e, effectively reduced methamphetamine-induced hyperactivity and mescaline-induced scratching, demonstrating dose-dependent effects. These findings highlight the modulators' selective action on the metabotropic glutamate receptor 2 and their favorable pharmacokinetic profiles, paving the way for innovative therapies in neuroscience and neuropharmacology research focused on receptor mechanisms and signaling.
Abstract
A novel series of mGluR2 positive allosteric modulators (PAMs), 1-[(1-methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines, is herein disclosed. Structure-activity relationship studies led to potent, selective mGluR2 PAMs with excellent pharmacokinetic profiles. A representative lead compound (+)-17e demonstrated dose-dependent inhibition of methamphetamine-induced hyperactivity and mescaline-induced scratching in mice, providing support for potential efficacy in treating psychosis.