title: In vivo effectiveness of CGP7930, a positive allosteric modulator of the GABAB receptor.
abstract: The present study was aimed at assessing the in vivo effectiveness of the positive allosteric modulator of the gamma-aminobutyric acidB (GABAB) receptor, CGP7930 [2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol]. The synergistic potentiation of GABAB receptor functioning, previously observed in different in vitro assays, has been confirmed in the present work, where pretreatment with CGP7930 (10-170 mg/kg, i.p.) resulted in a marked potentiation of the sedative/hypnotic effect of the GABAB receptor agonists, baclofen (40 mg/kg, i.p.) and gamma-hydroxybutyric acid (500 mg/kg, i.p.), in DBA mice. Pretreatment with the GABAB receptor antagonist, SCH 50911 [(S)-5,5-dimethyl-2-morpholine acetic acid; 100 mg/kg, i.p.], resulted in a complete blockade of the sedative/hypnotic effect of the combination of CGP7930 with either baclofen or gamma-hydroxybutyric acid. These results confirm that CGP7930 may constitute an interesting tool for pharmacological studies in the GABAB receptor field.
authors.affiliation: Bernard B. Brodie Department of Neuroscience, University of Cagliari, Viale Diaz 182, I-09126 Cagliari (CA), Italy. macarai@unica.it
authors.forename: Mauro A M
authors.initials: MA
authors.lastname: Carai
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Froestl
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
mesh_terms: D000818:Animals; D001418:Baclofen; D004357:Drug Synergism; D018755:GABA Agonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009025:Morpholines / Q000494:pharmacology; D010636:Phenols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018080:Receptors, GABA-B / Q000187:drug effects*; D012978:Sodium Oxybate / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; C438607:2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol; D018755:GABA Agonists; D058788:GABA-B Receptor Antagonists; D006993:Hypnotics and Sedatives; D009025:Morpholines; D010636:Phenols; D018080:Receptors, GABA-B; D012978:Sodium Oxybate; D001418:Baclofen