Gamma-guanidinobaclofen is a peripheral GABAB receptor agonist.
In the guinea-pig isolated ileum, both baclofen and gamma-guanidinobaclofen elicited dose-dependent depression of cholinergic twitch contractions, sensitive to the GABAB receptor antagonists phaclofen and 2-hydroxysaclofen. 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 maintained in Mg(2+)-free medium, baclofen (1-50 microM) reduced the amplitude and rate, whilst gamma-guanidinobaclofen (1 mM) has a very weak GABAB receptor agonist action, 100 times weaker than baclofen. gamma-Guanidinobaclofen is therefore a GABAB receptor agonist, more potent at peripheral than central GABAB receptors.
Kerr
D I
DI
Department of Anaesthesia and Intensive Care, University of Adelaide, Australia.
Humeniuk
R E
RE
Ong
J
J
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects; D003337:Corpus Callosum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; C091422:gamma-guanidinobaclofen; D001418:Baclofen; C057491:2-hydroxysaclofen