Evaluation of peripheral versus central effects of GABA(B) receptor activation using a novel, positive allosteric modulator of the GABA(B) receptor ADX71943, a pharmacological tool compound with a fully peripheral activity profile.

ABSTRACT:

Background and purpose

The GABA(B) receptor agonist, baclofen, has shown promising effects in patients suffering from pain, post-traumatic stress disorder, alcoholism, overactive bladder and gastroesophageal reflux disease. However, baclofen's short duration of action and side effects limit its wider use. Here we characterized a novel, GABA(B) receptor positive allosteric modulator (PAM) ADX71943.

Experimental approach

In vitro, ADX71943 was assessed for pharmacological activity and selectivity using recombinant and native GABA(B) receptors. In vivo ADX71943 was assessed in the acetic acid-induced writhing (AAW) test in mice and formalin tests (FTs) in mice and rats. Marble burying (MB) and elevated plus maze (EPM) tests, rotarod, spontaneous locomotor activity (sLMA) and bo

SUBMITTER: Kalinichev M 

PROVIDER: S-EPMC4294116 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature