Picrotoxin GABAa receptor binding

Experimentally all GABA antagonists induce convulsions. These include the genuine receptor antagonist bicuculline, which competes with GABA for its recognition site on the GABAa receptor and picrotoxin, which binds to a different site more closely related to the chloride ion channel. 

A. Analeptic stimulants, such as pentylenetetrazol and picrotoxin, act by inhibiting chloride influx at the GABAa receptor-chloride channel complex. This antagonism can occur through interaction with one of several binding sites or allosteric modifiers of receptor-channel function. 

The neuroexcitatory properties of toxaphene are due to its ability to reduce chloride uptake into neurons, leading to depolarization of the cells and hyperactivity. It is believed that toxaphene acts on the picrotoxin-binding site on the GABAa receptor. 

Watt 62), one of the earlier researchers to recognize the potential of African plants in improving mental health, reported the use of Cotyledon orbiculata (Crassulaceae) leaves to treat epilepsy. Again, in vivo studies have demonstrated both aqueous and methanol extracts of C. orbiculata have anticonvulsant properties (moderate protection against pentylenetetrazole, bicuculline, picrotoxin and A-methyl-dl-aspartic induced seizures in mice) 63). However, the ethanolic extract did not show in vitro GABAA-benzodiazepine receptor binding activity 64). 

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