GAMMA-GUANIDINOBACLOFEN IS A PERIPHERAL GABA(B) RECEPTOR AGONIST

In the guinea-pig isolated ileum, both baclofen and gamma-guanidinobac lofen elicited dose-dependent depression of cholinergic twitch contrac tions, sensitive to the GABA(B) receptor antagonists phaclofen and 2-h ydroxysaclofen. gamma-Guanidinobaclofen was 5 times less potent than R ,S-(+)-baclofen in depressing the contractions. The corresponding GABA analogs, guanidinoacetic acid, beta-guanidinopropionic acid and gamma -guanidinobutanoic acid were inactive. In rat neocortical slices maint ained in Mg2+-free medium, baclofen (1-50 mu M) reduced the amplitude and rate, whilst gamma-guanidinobaclofen (1 mM) has a very weak GABA(B ) receptor agonist action, 100 times weaker than baclofen. gamma-Guani dinobaclofen is therefore a GABA(B) receptor agonist, more potent at p eripheral than central GABA(B) receptors.