Nelson Rachael M, Green A Richard, Hainsworth Atticus H
Pharmacology Research Group, School of Pharmacy, De Montfort University, LE1 9BH, Leicester, UK.
Eur J Pharmacol. 2002 Oct 11;452(3):255-62. doi: 10.1016/s0014-2999(02)02233-1.
Clomethiazole is a gamma-aminobutyric acid (GABA)-mimetic agent with anticonvulsant, sedative and neuroprotective properties. The pharmacological actions of clomethiazole that underlie its functional profile have not been fully explored, but are known to result from an interaction with the GABA(A) receptor. Here, we present a quantitative electrophysiological study of clomethiazole action at human recombinant GABA(A) receptors. Whole-cell currents were recorded from murine L(tk-) cells stably transfected with either alpha1, beta1 and gamma 2 or alpha1, beta2 and gamma 2 GABA(A) receptor subunits. Clomethiazole directly activated GABA(A) currents in alpha1/beta1/gamma 2- and alpha1/beta2/gamma 2-containing cells, with EC(50) values of 0.3 and 1.5 mM, respectively. A low concentration of clomethiazole (30 micro M) also potentiated the action of GABA in both cell types, equivalent to a 3-fold increase in potency and up to 1.8-fold increase in maximal current. Both direct activation and gamma-aminobutyric acid potentiation are likely to contribute to the in vivo profile of clomethiazole.
氯美噻唑是一种具有抗惊厥、镇静和神经保护特性的γ-氨基丁酸（GABA）模拟剂。氯美噻唑产生其功能特征的药理作用尚未得到充分研究，但已知是由于与GABA(A)受体相互作用所致。在此，我们展示了氯美噻唑对人重组GABA(A)受体作用的定量电生理研究。从稳定转染了α1、β1和γ2或α1、β2和γ2 GABA(A)受体亚基的小鼠L(tk-)细胞中记录全细胞电流。氯美噻唑直接激活含α1/β1/γ2和α1/β2/γ2的细胞中的GABA(A)电流，其半数有效浓度（EC(50)）值分别为0.3 mM和1.5 mM。低浓度的氯美噻唑（30 μM）也增强了两种细胞类型中GABA的作用，相当于效力增加3倍，最大电流增加高达1.8倍。直接激活和γ-氨基丁酸增强作用可能都对氯美噻唑的体内作用特征有贡献。
