Picrotoxin is a noncompetitive antagonist of γ-aminobutyric acid-A (GABA_A) and GABA_C receptors, with IC50 value of 0.6 μM for GABA_C receptors [1, 2].?

Three classes of GABA receptors have been characterized based on their pharmacology, namely GABA_A, GABA_B and GABA_C receptors, among which GABA_A and GABA_C receptors are ligand-gated chloride (Cl^-) channels. GABA receptors play important roles in central nervous system by responding to the inhibitory neurotransmitter GABA [2].?

In hippocampal cultured neurons, picrotoxin blocked GABA_A-mediated currents, with an IC50 of 14 μM. Bath application of picrotoxin at 7 μM induced epileptiform activity, by blocking 30% of the GABA_A-mediated receptor responses [1].?

In male rats, i.p. injection (3 mg/kg) of picrotoxin significantly increased somatostatin (SRIF) release from the median eminence (ME) compared to baseline levels measured in the same animals, whilst local perfusion of picrotoxin did not affect SRIF release from the ME, which suggested a physiological endogenous inhibitory tone of GABA on SRIF release [3].?

References:

[1]. Gibbs III J W, Sombati S, DeLorenzo R J, et al. Physiological and pharmacological alterations in postsynaptic GABA(A) receptor function in a hippocampal culture model of chronic spontaneous seizures. Journal of Neurophysiology, 1997, 77(4): 2139-2152.

[2]. Goutman J D, Calvo D J. Studies on the mechanisms of action of picrotoxin, quercetin and pregnanolone at the GABA rho 1 receptor. British Journal of Pharmacology, 2004, 141(4): 717-727.

[3]. Arancibia S, Briozzo P. Peripheral administration of picrotoxin and bicuculline stimulates in vivo somatostatin release from rat median eminence. Neuroscience Letters, 1990, 111(1-2): 211-216.