Wong E H, Snowman A M, Leeb-Lundberg L M, Olsen R W
Eur J Pharmacol. 1984 Jul 13;102(2):205-12. doi: 10.1016/0014-2999(84)90252-8.
Barbiturates and the related depressant drugs, etazolate and etomidate, inhibited both the binding of [3H]bicuculline methochloride (BMC) to gamma-aminobutyric acid (GABA) receptor sites and the binding of [3H] beta-carboline-3-carboxylic acid methyl ester (beta CCM) to benzodiazepine receptor sites in mammalian brain. These concentration-dependent effects were chemically specific and stereospecific in a manner correlating with the activity of barbiturates to enhance GABA responses in neurons and to enhance GABA and benzodiazepine receptor agonist binding in vitro. The barbiturate inhibition of [3H]BMC binding involved a decrease in affinity which at high concentrations of barbiturates results in an effective complete loss of detectable binding. The maximal inhibition of [3H] beta CCM binding involved a more modest decrease in affinity (increase in KD from 1.35 to 1.85 nM). The barbiturate inhibitions of both ligands could be reversed by picrotoxin, suggesting an indirect action at previously defined picrotoxin/barbiturate modulatory sites on the GABA-benzodiazepine receptor/chloride ion channel complex.
巴比妥类药物以及相关的抑制性药物乙唑酯和依托咪酯，抑制了[³H]荷包牡丹碱甲氯化物（BMC）与哺乳动物脑内γ-氨基丁酸（GABA）受体位点的结合，以及[³H]β-咔啉-3-羧酸甲酯（βCCM）与苯二氮䓬受体位点的结合。这些浓度依赖性效应具有化学特异性和立体特异性，其方式与巴比妥类药物增强神经元中GABA反应以及在体外增强GABA和苯二氮䓬受体激动剂结合的活性相关。巴比妥类药物对[³H]BMC结合的抑制涉及亲和力的降低，在高浓度巴比妥类药物作用下，可导致可检测到的结合有效完全丧失。对[³H]βCCM结合的最大抑制涉及亲和力更适度的降低（解离常数KD从1.35 nM增加到1.85 nM）。两种配体的巴比妥类药物抑制作用均可被印防己毒素逆转，这表明其对GABA-苯二氮䓬受体/氯离子通道复合物上先前确定的印防己毒素/巴比妥类药物调节位点具有间接作用。
