ADX71441, a novel, potent and selective positive allosteric modulator of the GABA(B) receptor, shows efficacy in rodent models of overactive bladder.

ABSTRACT:

Background and purpose

The GABAB receptor agonist baclofen reduces urethral resistance and detrusor overactivity in patients with spasticity. However, baclofen's side effects limit its use for the treatment of overactive bladder (OAB). Here, we tested a novel GABAB positive allosteric modulator (PAM) ADX71441 in models of OAB in mice and guinea pigs.

Experimental approach

Mice were left untreated or given (p.o.) vehicle (1% CMC), ADX71441 (1, 3, 10 mg kg(-1) ) or oxybutynin (100 mg kg(-1) ; Experiment 1) or vehicle (1% CMC), baclofen (1, 3, 6 mg kg(-1) ) or oxybutynin (Experiment 2). Treated mice were then overhydrated with water, challenged with furosemide, before being placed into micturition chambers and monitored for urinary parameters. In anaesthetized guinea pigs, intr

SUBMITTER: Kalinichev M 

PROVIDER: S-EPMC3925038 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature