Lapin I P
Neurosci Biobehav Rev. 1983 Summer;7(2):107-18. doi: 10.1016/0149-7634(83)90013-1.
Kynurenine, an endogenous cerebral and peripheral neuroactive metabolite of 1-tryptophan, exerts stimulant and convulsant effects in mice, rats and frogs. In mice it (intracerebroventricularly, ICV) antagonized the anticaffeine effect of diazepam and in smaller doses potentiated its sedative action. In rats 1-kynurenine (ICV) potentiated the convulsant action of caffeine. The effect of pentylenetetrazol was not altered in either species. The convulsant effect of 1-kynurenine is the most resistant among various convulsants towards the protective action of diazepam. The structure of 1-kynurenine is similar to benzophenones, metabolites of diazepam, and has four structural fragments common with diazepam. Putative endogenous and non-endogenous ligands of the benzodiazepine receptors have from one to three of these common fragments. Among the antagonists of diazepam exhibiting stimulant and convulsant action ethyl-beta-carboline-3-carboxylate has the same four fragments, Ro 5-3663 and Ro 15-1788 have three and caffeine two. The most striking dissimilarity is a diazo-moiety (N-C-C-N or N-C=C-C=N) absent in the structure of 1-kynurenine. This moiety seems to be the most important for the binding to the benzodiazepine receptors. A role of each fragment and their combinations as well as the stereoconfiguration for the pharmacological activity is considered. It is suggested that 1-kynurenine is a putative endogenous modulator or, less probably, ligand of the benzodiazepine receptor of either type (most probably that which mediates anxiolytic action of benzodiazepines) or a part of this receptor. The benzodiazepine receptor might be a phylogenetically transformed kynurenine receptor. Highly selective antagonism of purines to 1-kynurenine suggests that it can modulate the function of the benzodiazepine receptors via purinergic mechanisms. Stimulant and convulsant action of 1-kynurenine can be related to a moiety of succinic acid (O=C-C-C-C=O) which is typical of quinolinic acid, the strongest endogenous convulsant among kynurenines, and aspartic acid, an excitatory amino acid. 1-Kynurenine is suggested to be an anxiogenic and convulsigenic endogenous factor.
犬尿氨酸是色氨酸的一种内源性脑和外周神经活性代谢产物，对小鼠、大鼠和青蛙具有兴奋和惊厥作用。在小鼠中，它（脑室内注射，ICV）拮抗地西泮的抗咖啡因作用，小剂量时增强其镇静作用。在大鼠中，1-犬尿氨酸（ICV）增强咖啡因的惊厥作用。两种动物中戊四氮的作用均未改变。1-犬尿氨酸的惊厥作用在各种惊厥剂中对苯二氮䓬类药物的保护作用最具抗性。1-犬尿氨酸的结构与地西泮的代谢产物二苯甲酮相似，与地西泮有四个共同的结构片段。苯二氮䓬受体的假定内源性和非内源性配体具有这些共同片段中的一至三个。在表现出兴奋和惊厥作用的地西泮拮抗剂中，β-咔啉-3-羧酸乙酯有相同的四个片段，Ro 5-3663和Ro 15-1788有三个，咖啡因有两个。最显著的不同之处是1-犬尿氨酸结构中不存在重氮部分（N-C-C-N或N-C=C-C=N）。这个部分似乎对与苯二氮䓬受体的结合最为重要。考虑了每个片段及其组合以及立体构型对药理活性的作用。有人提出1-犬尿氨酸是一种假定的内源性调节剂，或者不太可能是任一类型苯二氮䓬受体（很可能是介导苯二氮䓬类药物抗焦虑作用的那种受体）的配体，或者是该受体的一部分。苯二氮䓬受体可能是一种系统发育上转化的犬尿氨酸受体。嘌呤对1-犬尿氨酸的高度选择性拮抗作用表明它可以通过嘌呤能机制调节苯二氮䓬受体的功能。1-犬尿氨酸的兴奋和惊厥作用可能与琥珀酸部分（O=C-C-C-C=O）有关，这是喹啉酸（犬尿氨酸中最强的内源性惊厥剂）和天冬氨酸（一种兴奋性氨基酸）的典型特征。有人提出1-犬尿氨酸是一种致焦虑和致惊厥的内源性因子。
