Picrotoxin

Picrotoxin, also known as cocculin, is a poisonous crystalline plant compound, first isolated by Pierre Boullay in 1812. The name "picrotoxin" is a combination of the Greek words "picros" (bitter) and "toxicon" (poison).

Found primarily in the fruit of the climbing plant Anamirta cocculus, it has a strong physiological action. It acts as a non-competitive channel blocker for the GABA_A receptor chloride channels. It is therefore a channel blocker rather than a receptor antagonist.

On the other hand, evidence exists that picrotoxin acts as a competitive antagonist, and not as a channel blocker. For example, Newland and Cull-Candy (1992) found that when recording GABA-activated currents in neurons, picrotoxin "did not alter the amplitude of the main conductance state. However, picrotoxin did reduce the frequency of channel openings." They concluded, "Our data are consistent with a mechanism whereby picrotoxin binds preferentially to an agonist bound form of the receptor and stabilizes an agonist-bound shut state. This could, for example, mean that picrotoxin enhances the occurrence of a desensitized state or an allosterically blocked state."