In vivo effectiveness of CGP7930, a positive allosteric modulator of the GABAB receptor.

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.