Braestrup C, Schmiechen R, Neef G, Nielsen M, Petersen E N
Science. 1982 Jun 11;216(4551):1241-3. doi: 10.1126/science.6281892.
The gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex, which is composed of distinct proteins embedded in the neuronal plasma membrane, is important for several effects of benzodiazepines, including protection afforded against convulsions. During structural modification of ethyl beta-carboline-3-carboxylate an agent was discovered which has high affinity for brain benzodiazepine receptors but which is a potent convulsant. Also in contrast to benzodiazepines, this type of benzodiazepine receptor ligand favors benzodiazepine receptors in the non-GABA-stimulated conformation, which may explain the convulsive properties.
γ-氨基丁酸(GABA)-苯二氮䓬受体复合物由嵌入神经元质膜的不同蛋白质组成,对苯二氮䓬的多种效应很重要,包括对惊厥的保护作用。在对β-咔啉-3-羧酸乙酯进行结构修饰的过程中,发现了一种对脑苯二氮䓬受体具有高亲和力但却是强效惊厥剂的物质。而且与苯二氮䓬不同的是,这类苯二氮䓬受体配体更倾向于非GABA刺激构象的苯二氮䓬受体,这可能解释了其惊厥特性。