Send to

Choose Destination
See comment in PubMed Commons below
ACS Med Chem Lett. 2010 Nov 11;1(8):433-438. Epub 2010 Aug 13.

Discovery of N-Aryl Piperazines as Selective mGlu(5) Potentiators with Efficacy in a Rodent Model Predictive of Anti-Psychotic Activity.

Author information

Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA ; Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.


This Letter describes the discovery, SAR and in vitro and in vivo pharmacological profile of a novel non-MPEP derived mGlu(5) positive allosteric modulator (PAM) based upon an N-aryl piperazine chemotype. This mGlu(5) chemotype exhibits the ability to act as either a non-competitive antagonist/negative allosteric modulator (NAM) or potentiator of the glutamate response depending on the identity of the amide substituent, i.e., a 'molecular switch'. A rapidly optimized PAM, 10e (VU0364289), was shown to be potent and specific for the rat mGlu(5) receptor and subsequently demonstrated to be efficacious in a clinically relevant rodent model predictive of anti-psychotic activity, thus providing the first example of a centrally active mGluR(5) PAM optimized from an HTS-derived mGluR5 competitive antagonist.

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Support Center