4-amino-3-hydroxybutanoic acid (GABOB)の体内代謝と中枢抑制作用に関する研究―特に光学異性体についての比較検討―

1) 1-(14)C labelled (3R)-(-)-4-amino-3-hydroxybutanoic acid (l-GABOB) and (3S)-(+)-4-amino-3-hydroxybutanoic acid (d-GABOB) were prepared from their racemic compound using camphor-10-sulfonic acid. These optical isomers were administered at the dose of 5.6μCi(1mg) to mice intraperitoneally and observed that l-GABOB was uptaken more rapidly into blood and organs, and metabolized more rapidly in the liver and kidney than d-GABOB, and that l-GABOB could penetrate significantly into the brain, while d-GABOB could hardly do it. 2) These substances in the concentration of 10(-3)M were topically applied on the epileptogenic focus of the cat cerebral cortex induced by potassium benzyl penicillin. As the results of the experiment, no more spike was observed several minutes after l-GABOB administration (n=6, all cases). On the contrary, the optical isomer, d-GABOB, showed a very weakly effect (Spike counts were reduced to 64.5±3.8%, n=6, P<0.05), and racemic GABOB moderately (Spike counts were reduced to 16.4±5.5%, n=6, P<0.05). 3) These substances were applied on the giant neurone, identified subesophageal ganglia of the african giant snail (Achatina fulica Ferussac) by bath-application method and microdropapplication method. As the results of the experiment, it was clarified that l-GABOB inhibited more strongly the electrical activity of the neurone than d-GABOB did it.