Effects of single intraperitoneal injections of an extract of Ginkgo biloba (EGb 761) and its terpene trilactone constituents on barbital-induced narcosis in the mouse

A mouse model of barbital-induced narcosis was used to examine the effects of single intraperitoneal injections of an extract of Ginkgo biloba (EGb 76 1), an extract devoid of terpene trilactones (CP 205), and three terpene tr ilactone constituents of the extract (ginkgolides A and B, bilobalide). Adm inistration of sodium barbital (180 mg/kg, IF) to the mice caused narcosis, measured as a loss in righting reflex. Single injections of EGb 761 (25 an d 50 mg/kg), given 60 min prior to sodium barbital, significantly shortened barbital-induced sleeping time, whereas these same doses of CP 205 were in effective. Single injections of ginkgolide B (1 mg/kg) and bilobalide (2 an d 5 mg/kg) significantly shortened sleeping time, whereas ginkgolide A was ineffective. The effects of ginkgolide B and bilobalide were reflected as i ncreases in latency to onset of sleep and those of EGb 761, ginkgolide B, a nd bilobalide were correlated with decreases in the number of mice that sle pt. At the behavioral level, these potent in vivo effects of EGb 761, ginkg olide B, and bilobalide resemble those of certain antidepressants. At the m olecular level, it is hypothesized that interactions with the picrotoxinin/ TBPT site of GABA-regulated Cl- channels of the CNS may be involved. This i nformation appears useful in explaining the clinically observed "vigilance- enhancing" and "antidepressant-like" actions of EGb 761. (C) 1999 Elsevier Science Inc. All rights reserved.