VU0364289

VU0364289 is a highly selective mGlu5 positive allosteric modulator (PAM) (binds to the MPEP (HY-14609A) 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[1][2][3].

Signaling Pathways >> GPCR/G Protein >> mGluR

Research Areas >> Neurological Disease

mGlu5:1.6 μM (EC50)

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]. Animal Model: Adult male Sprague-Dawley rats (250-275 g)[1]. Dosage: 10, 30, 56.6, 100 mg/kg Administration: Intraperitoneal injection; once. Result: Showed activity of reversing the hyperlocomotion induced by amphetamine, and can also significantly fewer ambulations in rats when dose up to 56.6 mg/kg. Animal Model: Adult male Sprague-Dawley rats (250-275 g)[1]. Dosage: 10 mg/kg Administration: Intraperitoneal injection; once. Result: 1.19Pharmacokinetic Parameters of VU0364289 in male Sprague-Dawley rats[1]. Tmax (h) Cmax (ng/mL) Plasma protein binding Rat Fu (free fraction) IP (10 mg/kg) 0.25 1280 94% (h); 90% (r) 0.10

[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.