Ginkgolides A, B, and C are diterpene trilactones and active constituents of the 50:1 Ginkgo biloba leaf extract widely used in the symptomatic treatment of mild to moderate dementia. Using the two-electrode voltage clamp methodology, these ginkgolides were found to be moderately potent antagonists at recombinant human α 1 β 2 γ 2 L GABA A receptors expressed in Xenopus oocytes. Ginkgolides A, B, and C inhibited the direct action of γ-aminobutyric acid (GABA) with K i values of 14.5+/-1.0, 12.7+/-1.7, and 16.3+/-2.4 μM respectively. Antagonism by these ginkgolides at α 1 β 2 γ 2 L GABA A receptors appears to be noncompetitive as indicated by the nonparallel right shift and reduced maximal GABA response in their GABA concentration-effect curves.