title: Acute toxicity of synthetic Gymnodinium breve toxin metabolite and its analogues in mice.
abstract: Acute toxicity of synthetic Gymnodinium breve toxin metabolite and its analogues has been investigated in mice. The anticholinesterase potencies of the toxin metabolite and its analogues were determined in vitro as well as in vivo. The intraperitoneal LD50 of the parent metabolite O,O-dipropyl(E)-2-(1-methyl-2-oxopropylidene) phosphorohydrazidothioate(E)oxime in mice was higher compared to LD50 values of its analogues. The in vitro acetylcholinesterase (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 AChE in vivo, whereas higher toxicity is associated with other analogues, suggesting the involvement of other factors influencing the toxicity, which needs to be further investigated.
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
authors.forename: K
authors.initials: K
authors.lastname: Husain
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: M P
authors.initials: MP
authors.lastname: Kaushik
authors.forename: A K
authors.initials: AK
authors.lastname: Gupta
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D004141:Dinoflagellida / Q000378:metabolism*; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008297:Male; D008387:Marine Toxins / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D010084:Oxidation-Reduction; D011041:Poisoning / Q000401:mortality; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D008387:Marine Toxins; D002802:Cholinesterases