Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Curr Top Med Chem. 2012;12(4):333-51. doi: 10.2174/156802612799078766.
The mitochondrial translocator protein (TSPO) mediates the synthesis of neurosteroids in the CNS, which have been demonstrated to enhance the neurotransmitter GABA response, exhibiting related behavioural properties. Selective TSPO ligands are able to stimulate steroidogenesis with great efficacy, thus representing potential anxiolytic agents. This review describes the development of a class of high affinity ligands to TSPO, N,N-dialkylindol-3-ylglyoxylamides (IGA), from the initial stages of design to the pharmacological characterization of selected compounds for their anxiolytic activity. Affinity data and SARs of the new class of ligands are discussed; the potential applications of compounds characterized by the indolylglyoxylyl scaffold in diagnostic imaging are also pointed out.
线粒体转位蛋白（TSPO）介导中枢神经系统中神经甾体的合成，已证明神经甾体能增强神经递质 GABA 的反应，表现出相关的行为特性。选择性 TSPO 配体能够非常有效地刺激甾体生成，因此代表了潜在的抗焦虑药物。本综述描述了一类高亲和力的 TSPO 配体，N,N-二烷基吲哚-3-基甘氨酸酰胺（IGA），从最初的设计阶段到对选定化合物的抗焦虑活性的药理学特征的描述。讨论了新配体类的亲和力数据和 SAR；还指出了由吲哚基甘氨酸骨架表征的化合物在诊断成像中的潜在应用。
