Isolation and inhibitory activity of gabaculine, a new potent inhibitor of gamma-aminobutyrate aminotransferase produced by a Streptomyces.

It is well known that GABA plays an inhibitory role in crustacean ans mammalian central nervous system [ 1,2]. Since GABA does not cross the blood-brain barrier, various inhibitors of GABA aminotransferase which cause an increase in its cerebral level have been introduced into this field of research [3-121. Most of these inhibitors are very toxic and not specific for GABA aminotransferase. During our search for new inhibitors of GABA aminotransferase from microbial origin, a potent inhibitor (designated as gabaculine) was found to be present in the culture of a Streptomyces. The present paper describes isolation and inhibitory activity of gabaculine. The results indicate that this new microbial metabolite is a potent, competitive inhibitor of GABA aminotransferase from both beef brain and Pseudomonas ovalis, having Ki values of 0.37-0.80 PM. The physicochemical properties and identification of chemical structure of gabaculine have been reported elsewhere [13].