title: CGP 52432: a novel potent and selective GABAB autoreceptor antagonist in rat cerebral cortex.
abstract: As previously reported GABAB receptors are heterogeneous. Three pharmacologically distinct receptor subtypes mediating inhibition of gamma-aminobutyric acid (GABA), glutamate or somatostatin release, respectively, exist on axon terminals of rat cerebral cortex. We investigated the novel GABAB receptor antagonist, [3-[[(3,4-dichlorophenyl)methyl]amino]propyl](diethoxy-methyl) phosphinic acid (CGP 52432), on the above receptor subtypes. The effects of (-)-baclofen on the K(+)-evoked release of GABA, glutamate or somatostatin from rat cortical synaptosomes were antagonized by CGP 52432. The IC50 of the drug at GABA autoreceptors (0.085 microM) was 35- and 100-fold lower than at the receptors regulating somatostatin and glutamate overflow, respectively. At the autoreceptor the calculated pA2 for CGP 52432 amounted to 7.70, which makes the drug about 1000-fold more potent than phaclofen at this receptor. The potency and selectivity characteristics of CGP 52432 indicate that the drug is by far the most appropriate tool to investigate the terminal GABAB autoreceptors of the rat cerebral cortex.
authors.affiliation: Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Lanza
authors.forename: A
authors.initials: A
authors.lastname: Fassio
authors.forename: A
authors.initials: A
authors.lastname: Gemignani
authors.forename: G
authors.initials: G
authors.lastname: Bonanno
authors.forename: M
authors.initials: M
authors.lastname: Raiteri
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D058787:GABA-A Receptor Antagonists; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010721:Phosphinic Acids; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001596:Benzylamines; D058787:GABA-A Receptor Antagonists; D005971:Glutamates; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; C083008:CGP 52432; D018698:Glutamic Acid; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D001418:Baclofen