Acute Toxicity of SyntheticGymnodinium breveToxin Metabolite and Its Analogues in Mice

Acute toxicity of syntheticGymnodinium brevetoxin metabolite and its analogues has been investigated in mice. The anticholinesterase potencies of the toxin metabolite and its analogues were determinedin vitroas well asin vivo.The intraperitoneal LD50of the parent metaboliteO,O-dipropyl(E)-2-(1-methyl-2-oxopropylidene)phosphorohydrazidothioate(E)oxime in mice was higher compared to LD50values of its analogues. Thein vitroacetylcholinesterase (AChE)-inhibiting potency values were higher for diethoxy(P=O) analogue than for diispropoxy(P=O) analogue. Lethal doses of parent metabolite and its analogues significantly inhibited AChE activity in the blood and brain of mice 1 hr postexposure. The maximum inhibition by the parent metabolite was observed in both tissues. The percentage inhibition of AChE activity was greater in the blood than in the brain. The results indicate that these agents have anticholinesterase action specifically in the blood. In conclusion, the parent toxin metabolite is a more potent inhibitor of AChEin vivo,whereas higher toxicity is associated with other analogues, suggesting the involvement of other factors influencing the toxicity, which needs to be further investigated.