Picrodendrins, a New Group of Picrotoxane Terpenoids : Structur-Activity Profile of Action at the GABA_A Receptor-coupled Picrotoxinin Binding Site in Rat Brain

Abstract

Seven out of 20 assayed picrotoxane terpenoids inhibited specific binding of [³⁵S] t-butylbicyclophosphorothionate to rat brain membranes, with IC₅₀ values of 0. 0075-6. 0μM. Picrodendrin Q was identified as the most potent compound, being about 27-fold more potent than picrotoxinin. The high activity of picrodendrins A, M, and Q suggests the significance of the spiro α-ethylidene γ-lactone moiety for the interaction of picrodendrins with the GABAA receptor-coupled picrotoxinin binding site.