PROPHYLAXIS AGAINST SARIN POISONING IN THE RAT BY ORAL ADMINISTRATION OF 2-PAMC1

The aims of the present study were to (a) establish the parameters associated with oxime concentration in plasma following oral administration of 2-PAMC1 (2-pyridine aldoxime methochloride) to rats, (b) determine the combined effect of prophylaxis with 2-PAMC1 and treatment with atropine on the toxicity of sarin (isopropyl methylphosphonofluoridate, GB) in rats, and (c) establish a correlation between oxime level in plasma and protection afforded against sarin poisoning. It was concluded that: (1) When 2-PAMC1 is administered orally to rats, the plasma oxime level rises rapidly, reaches a maximum after about 1 hr, and then decreases at a first-order rate. The biological half-life of 2-PAMC1 in the rat is estimated to be 1.4 hr. (2) A prophylactic effect of 2-PAMC1, when used in conjunction with atropine, has been demonstrated in rats poisoned with sarin. (3) The protection afforded by 2-PAMC1 against sarin poisoning in rats can be correlated with the oxime level in the plasma at the time of sarin poisoning.