VU0364289

VU0364289 is a highly selective mGlu5 positive allosteric modulator (PAM) (binds to the MPEP site), with an EC50 of 1.6 µM. VU0364289 can reverse amphetamine-induced hyperlocomotion in a dose-dependent manner, which can be used for schizophrenia and other psychiatric research.

VU0364289 (10, 30, 56.6, 100 mg/kg ; i.p.; once) reverse amphetamine-induced hyperlocomotion in a dose-dependent manner, and (56.6, 100 mg/kg) shows significantly fewer ambulations^[1].
VU0364289 (10 mg/kg; i.p.; once) is rapidly and significantly absorbed in rats, and shows excellent central nervous system penetration^[1].

References:
[1]. Gregory KJ, et al. N-aryl piperazine metabotropic glutamate receptor 5 positive allosteric modulators possess efficacy in preclinical models of NMDA hypofunction and cognitive enhancement. J Pharmacol Exp Ther. 2013 Nov;347(2):438-57.
[2]. Ya Zhou, et al. Discovery of N-Aryl Piperazines as Selective mGluR5Potentiators with Improved In Vivo Utility. ACS medicinal chemistry letters, 2010, 1(8): 433-438.
[3]. Psychosis Models[M]//Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi, 2016: 731-750.