Harrison N L, Simmonds M A
Br J Pharmacol. 1983 Oct;80(2):387-94. doi: 10.1111/j.1476-5381.1983.tb10045.x.
Some pharmacological properties of the GABAA receptor complex in the rat cuneate nucleus slice have been assessed from depolarization responses to the gamma-aminobutyric acid (GABA) analogue muscimol and antagonism of the responses by bicuculline and picrotoxin. Responses to muscimol were potentiated by the following drugs, in descending order of potency with regard to the concentrations required in the Krebs medium: (+/-)-5-(1,3-dimethylbutyl)-5-ethylbarbituric acid [+/-)-DMBB) = (+/-)-quinalbarbitone = (+/-)-pentobarbitone greater than (+/-)-methyl-phenobarbitone = (-)-methylphenobarbitone greater than butobarbitone = chlormethiazole greater than phenobarbitone greater than barbitone = (+)-methylphenobarbitone. Primidone and phenylethylmalonamide were inactive. Calculation of the concentrations likely to be present in membrane lipids for equal potentiations of muscimol revealed little difference between quinalbarbitone, pentobarbitone, phenobarbitone and barbitone. The effect of picrotoxin as a muscimol antagonist was selectively reduced only by DMBB, chlormethiazole, phenobarbitone and (-)-methylphenobarbitone in concentrations that caused only a modest potentiation of muscimol. It is suggested that a specific site of action in the GABAA receptor complex is involved in the reduction of picrotoxin effect and that this may be relevant to the anticonvulsant properties of chlormethiazole, phenobarbitone and (-)-methylphenobarbitone. The potentiation of muscimol by chlormethiazole and the barbiturates in general involves a distinctly different site that is less selective and this may underlie the hypnotic properties of these drugs.
通过对大鼠楔束核切片中γ-氨基丁酸（GABA）类似物蝇蕈醇的去极化反应以及荷包牡丹碱和印防己毒素对该反应的拮抗作用，评估了GABAA受体复合物的一些药理学特性。对蝇蕈醇的反应被以下药物增强，按照在 Krebs 培养基中所需浓度的效力降序排列：(±)-5-(1,3-二甲基丁基)-5-乙基巴比妥酸[(±)-DMBB] = (±)-速可巴比妥 = (±)-戊巴比妥＞(±)-甲基苯巴比妥 = (-)-甲基苯巴比妥＞布他比妥 = 氯美噻唑＞苯巴比妥＞巴比妥 = (+)-甲基苯巴比妥。扑米酮和苯乙丙二酰胺无活性。计算在膜脂中可能存在的、能使蝇蕈醇等电位增强的浓度，发现速可巴比妥、戊巴比妥、苯巴比妥和巴比妥之间差异不大。仅在引起蝇蕈醇适度增强的浓度下，印防己毒素作为蝇蕈醇拮抗剂的作用仅被 DMBB、氯美噻唑、苯巴比妥和(-)-甲基苯巴比妥选择性降低。提示GABAA受体复合物中的一个特定作用位点参与了印防己毒素作用的降低，这可能与氯美噻唑、苯巴比妥和(-)-甲基苯巴比妥的抗惊厥特性有关。氯美噻唑和巴比妥类药物对蝇蕈醇的增强作用一般涉及一个选择性较低的明显不同的位点，这可能是这些药物催眠特性的基础。
