ACUTE TOXICITY OF SYNTHETIC GYMNODINIUM BREVE TOXIN METABOLITE AND ITS ANALOGS IN MICE

Acute toxicity of synthetic Gymnodinium breve toxin metabolite and its analogues has been investigated in mice. The anticholinesterase poten cies of the toxin metabolite and its analogues were determined in vitr o as well as in vivo. The intraperitoneal LD(50) of the parent metabol ite ethyl-2-oxopropylidene)phosphorohydrazidothioate(E )oxime in mice was higher compared to LD(50) values of its analogues. The in vitro ac etylcholinesterase (AChE)-inhibiting potency values were higher for di ethoxy(P=O) analogue than for diispropoxy(P=O) analogue. Lethal doses of parent metabolite and its analogues significantly inhibited AChE ac tivity in the blood and brain of mice 1 hr postexposure. The maximum i nhibition by the parent metabolite was observed in both tissues. The p ercentage inhibition of AChE activity was greater in the blood than in the brain. The results indicate that these agents have anticholineste rase action specifically in the blood. In conclusion, the parent toxin metabolite is a more potent inhibitor of AChE in vivo, whereas higher toxicity is associated with other analogues, suggesting the involveme nt of other factors influencing the toxicity, which needs to be furthe r investigated. (C) 1996 Academic Press, Inc.