Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant α1 β2γ2L GABAA receptors

The sesquiterpene trilactone bilobalide is one of the active constituents of the 50:1 Ginkgo biloba leaf extract widely used to enhance memory and learning. Bilobalide was found to antagonise the direct action of gamma-aminobutyric acid (GABA) on recombinant alpha(1)beta(2)gamma(2L) GABA(A) receptors. The effect of bilobalide on the direct action of GABA at alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp method was evaluated and compared with the effects of the classical GABA(A) receptor competitive antagonist bicuculline and noncompetitive antagonist picrotoxinin. Bilobalide (IC50 = 4.6 +/- 0.5 muM) was almost as potent as bicuculline and pictrotoxinin (IC50 2.0 +/- 0.1 and 2.4 +/- 0.5 muM, respectively) at alpha(1)beta(2)gamma(2L) GABA(A) receptors against 40 muM GABA (GABA EC50). While bilobalide and picrotoxinin were clearly noncompetitive antagonists, the potency of bilobalide decreased at high GABA concentrations suggesting a component of competitive antagonism. (C) 2003 Elsevier Science B.V. All rights reserved.