VU0467154

Animal experiment:

Rats[1]To determine the relationship between in vivo efficacy of VU0467154 and brain concentrations in rats, the efficacy of VU0467154 (1, 3, 10, 30, and 56.6 mg/kg, PO; n ≥ 8 per dose level) in reversing amphetamine-induced hyperlocomotion is correlated to the brain concentrations of VU0467154 in the same animals upon study completion (1.5 h postadministration). In mice, the in vivo concentration-effect relationship for VU0467154 is determined by correlating the efficacy of VU0467154 in reversing amphetamine-induced hyperlocomotion (0.3, 1, 3, 10, and 30 mg/kg, IP) to the brain concentrations of VU0467154 in the same animals upon study completion (2.5 h postadministration). Terminal unbound brain concentrations for all treatment groups are plotted versus each animal’s efficacy in reversing amphetamine-induced hyperlocomotion. Nonlinear regression analysis of the plotted data are calculated to determine the in vivo EC50 value (nM) for VU0467154 in reversing amphetamine-induced hyperlocomotion in rats using GraphPad Prism 5.0[1].

References:

[1]. Bubser M, et al. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci. 2014 Oct 15;5(10):920-42.