Picrotoxinin is a bitter toxin derived from natural plants; it is found in the seeds of a climbing plant known as Anamirta cocculus and acts as a chloride channel blocker[1, 2]. Picrotoxinin is a non-competitive antagonist of the GABAA receptor, negatively modulating the effects of the neurotransmitter gamma-aminobutyric acid (GABA) on GABAA receptors[3]. Picrotoxinin is a potent convulsant[4].
In vitro, treatment of Xenopus laevis oocytes with Picrotoxinin (0.001μM-1mM) for 90s inhibited GABA-induced chloride currents in a concentration-dependent manner; furthermore, it blocked the opening of chloride channels induced by various positive allosteric modulators (etomidate, propofol, diazepam, thiopentone sodium, loreclezole, and allopregnanolone)[5].
References:
[1] Katsnelson A. Making Natural Products Supernatural[J]. 2024.
[2] Olsen R W. Picrotoxin-like channel blockers of GABAA receptors[J]. Proceedings of the National Academy of Sciences, 2006, 103(16): 6081-6082.
[3] Das P, Bell-Horner C L, Machu T K, et al. The GABAA receptor antagonist picrotoxin inhibits 5-hydroxytryptamine type 3A receptors[J]. Neuropharmacology, 2003, 44(4): 431-438.
[4] Senghani M K, Patel P M, Sagar G V. Anticonvulsant activity of boswellic acids against maximal electroshock-induced convulsive rats and picrotoxin-induced convulsive mice[J]. Res J Pharmacon Phytochem, 2012, 4(6): 318-21.
[5] Ng C C, Duke R K, Hinton T, et al. Effects of bilobalide, ginkgolide B and picrotoxinin on GABAA receptor modulation by structurally diverse positive modulators[J]. European journal of pharmacology, 2017, 806: 83-90.