Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant alpha1beta2gamma2L GABA(A) receptors

Eur J Pharmacol. 2003 Mar 7;464(1):1-8. doi: 10.1016/s0014-2999(03)01344-x.

Abstract

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 (IC(50)=4.6+/-0.5 microM) was almost as potent as bicuculline and pictrotoxinin (IC(50)=2.0+/-0.1 and 2.4+/-0.5 microM, respectively) at alpha(1)beta(2)gamma(2L) GABA(A) receptors against 40 microM GABA (GABA EC(50)). While bilobalide and picrotoxinin were clearly noncompetitive antagonists, the potency of bilobalide decreased at high GABA concentrations suggesting a component of competitive antagonism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Cyclopentanes / pharmacology*
  • Diterpenes*
  • Dose-Response Relationship, Drug
  • Furans / pharmacology*
  • GABA Antagonists / pharmacology*
  • GABA-A Receptor Antagonists*
  • Ginkgo biloba / chemistry*
  • Ginkgolides
  • Humans
  • Membrane Potentials / drug effects
  • Oocytes / drug effects
  • Oocytes / physiology
  • Picrotoxin / analogs & derivatives*
  • Picrotoxin / pharmacology
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / physiology
  • Recombinant Proteins / antagonists & inhibitors
  • Sesterterpenes
  • Xenopus laevis
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Cyclopentanes
  • Diterpenes
  • Furans
  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • Ginkgolides
  • Receptors, GABA-A
  • Recombinant Proteins
  • Sesterterpenes
  • Picrotoxin
  • gamma-Aminobutyric Acid
  • picrotoxinin
  • bilobalide
  • Bicuculline