Neurochemical and neurophysiological mechanism for guanidino compoundinduced seizures

我们曾报道过将胍基化合物，如牛磺氰胺、胍乙酸<gamma>、胍丁酸、N-乙酰精氨酸、甲基胍和<alpha>胍谷氨酸（GGA）注入兔、狗、猫和大鼠脑池内，引起剧烈惊厥。本文的主要研究内容如下：1.在具有惊厥倾向的El小鼠的大脑皮质、小脑、中脑和延髓中观察到甲基胍水平升高。N-乙酰天冬氨酸诱导惊厥时脑内.在<gamma>戊四氮诱导的惊厥过程中，观察到家兔CSF中-胍基乙酸水平升高。GGA诱发的癫痫发作与脑内5-HT能功能异常有关，即脑内5-HT水平短暂性降低并促进其释放.高精氨酸和<alpha>-胍基戊酸诱导大鼠癫痫发作放电，当局部或脑池内给药。<alpha>- 胍基戊酸可能作为拮抗剂作用于GABA系统，诱发棘波放电.牛磺氰胺对惊厥有双极效应，即它能显著延迟二苯甲酰胍诱发的小鼠惊厥。另一方面，增加了未受刺激的小鼠惊厥的发生率。在正常人尿中发现一种新的胍基化合物<alpha>-胍基乙醇。给药大鼠脑内可诱发癫痫性脑电放电和惊厥.在给小鼠施用L-（脒基- &lt;^（15）N&gt; -精氨酸后，用&lt;^（15）N&gt; -分析仪观察到&lt;^（15）N&gt;在脑和肾中与胍基乙酸以及在肝中与胍基乙酸、甲基胍和胍基琥珀酸的结合。在癫痫患者的脑脊液中发现了高水平的牛磺氰胺。在人类癫痫患者的致痫灶组织中，牛磺氰胺、甲基胍和N-乙酰精氨酸的水平较高。

We have reported that guanidino compound, e.g. taurocyamine, guanidinoacetic acid, <gamma> -guanidinobutyric acid, N-acetylarginine, methylguanidine, and <alpha> -guanidinoglutaric acid(GGA), induced violent convulsions after intracisternal injection into rabbits, dogs, cats, and rats. The summary of the present studies is as follows:1. Increased levels of methylguanidine were observed in the cerebral cortex, cerebellum, midbrain, and medulla oblongata of El mice with a convulsive disposition. N-Acetylaspartic acid induced in the brain during convulsions.2. Increased levels of <gamma> -guanidinoacetic acid were observed in the rabbit CSF during pentylenetetrazol induced convulsions.3. GGA induced seizures were associated with an abnormal serotonergic function, i.e. the transitorily decreased level and facilitated release of 5-HT in the brain.4. Homoarginine and <alpha> -guanidinovaleric acid induced seizure discharges in rats, when administered topically or intracisternally. <alpha> -guanidinovaleric acid may act on a GABA system to induce spike discharges as an antagonist.5. Taurocyamine has bipolar effects on convulsions; i.e. it delayed markedly the dibenzoylguanidine-induced convulsions in mice. On the other hand, it increased the incidence of convulsion in the non-stimulated El-mice.6. A new guanidino compound, <alpha> -guanidinoethanol, was found in normal human urine. It induced epileptic EEG discharges and convulsions when administerd into the rat brain.7. Incoporation of a <^(15)N> into guanidinoacetic acid in the brain and kidney, and guanidinoacetic acid, methylguanidine and guanidinosuccinic acid in the liver, was observed with a <^(15)N> -analyser after the administration of L-(amidino- <^(15)N> -arginine into mice.8. A high level of taurocyamine was found in the CSF of epileptic patients. Higher levels of taurocyamine, methylguanidine and N-acetylarginine were demonstrated in the epileptogenic focus tissue of human epileptic patients.