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• W1930038814 abstract "1. Measurements of the acute toxicity of OMPA given intraperitoneally gave the following approximate LD50 values in mgm./kgm.: rats 8, mice 17, and guinea pigs 10. For dogs given OMPA intravenously the LD50 was between 5 and 10 mgm./kgm. When given orally to rats the approximate LD50 was 10 mgm./kgm. indicating that the compound is well absorbed from the gastro-intestinal tract. In rats no sex or age differences in susceptibility to OMPA were observed.2. The symptoms produced in all of the species studied were typical of those produced by parasympathomimetic drugs except that symptoms referable to central nervous system stimulation were absent.3. Large doses of OMPA injected intravenously in anesthetized dogs produced an immediate evanescent but non-specific fall in blood pressure and increase in respiratory rate followed by a gradual development of bradycardia and increase in pulse pressure culminating in cardiac failure.4. OMPA was ineffective as an anticholinesterase agent in vitro since it produced only 24 per cent inhibition of the cholinesterase of several tissues at a final concentration of 1 x 10-2 M. However in two hours after intraperitoneal administration of 5 mgm./kgm. to rats the following per cent inhibition of cholinesterase activity was noted: submaxillary 89, ileum 70, serum 87, skeletal muscle 68, and brain 2. After lethal doses of 15 mgm./kgm. the cholinesterase activity of peripheral tissues was about 90 per cent inhibited while brain was only 7 per cent inhibited thus indicating a selective action on peripheral cholinesterase.5. After 5 mgm./kgm. of OMPA was given intraperitoneally to rats a progressive decrease in cholinesterase activity occurred over a two-hour period which was consistent with a delayed onset of symptoms after administration of this compound.6. OMPA produced a reversible inhibition of cholinesterase in vivo but the duration of the inhibitory effect was somewhat longer than that produced by TEPP and Parathion. Considerable differences were observed in the rate of return of cholinesterase activity in various tissues.7. A cumulative toxic action was observed in rats after daily intraperitoneal administration of 1, 1.5, and 2 mgm./kgm. of OMPA. A progressive decrease in the cholinesterase activity of the tissues was observed with these doses. Rats were able to tolerate daily doses of 0.25 and 0.5 mgm./kgm. of OMPA for at least 60 days with no apparent untoward effects.8. The finding that OMPA is altered by the liver to a strong anticholinesterase agent offers an explanation for its unusual properties. Conversion by the liver to an anticholinesterase agent was demonstrated by incubation of OMPA aerobically with tissue slices in Krebs-Ringer-phosphate buffer containing 0.01 M glucose. Plants grown in soil containing OMPA were found to contain an anticholinesterase agent indicating that plants can also convert the material.9. Using the cholinesterase system as an assay method it was possible to study the rate of production and properties of the active metabolite formed from OMPA by liver slices.10. Atropine premedication in mice increased the LD50 of OMPA fourfold, and atropine-eserine premedication increased the LD50 elevenfold. Eserine itself in sublethal doses exhibited little prophylactic effect. Atropine therapy in dogs increased the LD50 about fourfold." @default.
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• W1930038814 date "1950-07-01" @default.
• W1930038814 modified "2023-09-23" @default.
• W1930038814 title "Studies on the toxicity and pharmacological action of octamethyl pyrophosphoramide (OMPA; Pestox III)." @default.
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