Ginkgolides, diterpene trilactones of Ginkgo biloba, as antagonists at recombinant alpha1beta2gamma2L GABAA receptors.
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 alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in Xenopus oocytes. Ginkgolides A, B, and C inhibited the direct action of gamma-aminobutyric acid (GABA) with K(i) values of 14.5+/-1.0, 12.7+/-1.7, and 16.3+/-2.4 microM respectively. Antagonism by these ginkgolides at alpha(1)beta(2)gamma(2L) 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.
Huang
Shelley H
SH
Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology, Faculty of Medicine, The University of Sydney, Sydney, NSW 2006, Australia.
Duke
Rujee K
RK
Chebib
Mary
M
Sasaki
Keiko
K
Wada
Keiji
K
Johnston
Graham A R
GA
D000818:Animals; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry*; D046934:Ginkgolides; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*; D011994:Recombinant Proteins / Q000187:drug effects; D054830:Sesterterpenes; D014982:Xenopus laevis
D004224:Diterpenes; D018756:GABA Antagonists; D046934:Ginkgolides; D007783:Lactones; D010852:Picrotoxin; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D054830:Sesterterpenes; C058295:ginkgolide C; C022961:picrotoxinin; C045856:ginkgolide B; C477042:ginkgolide A