GABA_B receptor allosteric modulators exhibit pathway-dependent and species-selective activity.

ABSTRACT: Positive modulation of the GABA_B receptor (GABA_BR) represents a potentially useful therapeutic approach for the treatment of nicotine addiction. The positive allosteric modulators (PAMs) of GABA_BR GS39783 and BHF177 enhance GABA-stimulated [³⁵S]GTP γS-binding, and have shown efficacy in a rodent nicotine self-administration procedure reflecting aspects of nicotine dependence. Interestingly, the structural related analog, NVP998, had no effect on nicotine self-administration in rats despite demonstrating similar pharmacokinetic properties. Extensive in vitro characterization of GS39783, BHF177, and NVP998 activity on GABA_BR-regulated signaling events, including modulation of cAMP, intracellular calcium levels, and ERK activation,

SUBMITTER: Sturchler E 

PROVIDER: S-EPMC5368958 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature