Enzymes as pretreatment drugs for organophosphate toxicity. (Reannouncement with new availability information)

Technical Report · Tue Dec 31 04:00:00 EST 1991

OSTI ID:91420

Doctor, B P; Raveh, L; Wolfe, A D; Maxwell, D L; Ashani, Y

We have successfully demonstrated that exogenously administered acetyl- or butyrylcholinesterase (AChE, BChE respectively) will sequester organophosphates (OPs) before they reach their physiological targets. In addition, a third enzyme, endogenous carboxylesterase is known to be capable of scavenging OPs. In these studies, we have administered AChE and BChE to three different species of animals (mice, marmosets and monkeys) which were challenged with three different OPs (VX, MEPQ and soman). Results obtained from these systematic studies demonstrate that: (a) a quantitative linear correlation exists between blood AChE levels and the protection afforded by exogenously administered ChEs in animals challenged with OPm (b) approximately one mole of either AChE or BChE sequesters one mole of OP, (c) such prophylactic measures are sufficient to protect animals against OPs without the administration of any supportive drugs. Thus the OP dose, the blood-level of esterase, the ratio of the circulating enzyme to OP challenge, and the rate of reaction between them determine the overall efficacy of an enzyme as a pretreatment drug.

• Research Organization: Walter Reed Army Inst. of Research, Washington, DC (United States)
• OSTI ID: 91420
• Report Number(s): AD-A--238916/1/XAB
• Country of Publication: United States
• Language: English

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