Reactivator Report for: DAM

The effects of monoisonitrosoacetone (MINA), diacetylmonoxime (DAM) and pyridine-2-aldoxime methiodide (P2AM) upon the cholinesterase of sarin poisoned rats have been studied. Monoisonitrosoacetone and diacetylmonoxime given before sarin protected blood and brain cholinesterase from inhibition. Monoisonitrosoacetone given after the appearance of signs of poisoning caused a rapid reactivation of brain cholinesterase. Diacetylmonoxime, at an equimolar dose, produced only a slight increase in enzyme activity, and pyridine-2-aldoxime methiodide, the best reactivator in vitro, reactivated blood but not brain cholinesterase. There is a relationship between protection and reactivation of brain cholinesterase and prevention and alleviation of signs of poisoning.

Three oximes, monoisonitrosoacetone (MINA), pyridine-2-aldoxime methiodide (PAM) and diacetylmonoxime (DAM), have been examined in combination with atropine as antidotes in sarin poisoning. When treatment was administered 15 min. before sarin, atropine enhanced the protective effect of MINA and DAM 2 to 3 times and of PAM 9 to 10 times in mice and rats. In mice, rats, and guinea-pigs, atropine increased by no more than 2 times the protective effect of all three oximes when given 30 sec. after sarin. Atropine given to monkeys 1 min. after sarin raised the LD50 approximately 3 times. When given in conjunction with MINA or DAM, the LD50 of sarin was raised 7 to 14 times.

The capability of the tertiary oximes, monoisonitrosoacetone (MINA) and diacetylmonoxime (DAM), to reactivate acetylcholinesterase (AChE) inhibited by sarin (GB) in the blood, brain, and peripheral tissues of guinea pigs was compared with that of the quaternary oximes 2-PAM, HLo7, and MMB-4. Animals were injected subcutaneously (s.c.) with 1.0 x LD(50) of GB and treated intramuscularly (i.m.) 5 min later with one of these oximes. Sixty minutes after GB exposure, tissues were collected for AChE analysis. At low doses, MINA and DAM produced significant increases in AChE activity in all brain areas examined, but no significant AChE reactivation in peripheral tissues or blood. At higher doses, MINA and DAM increased AChE activity in the brain, peripheral tissues, and blood. In contrast, the quaternary oximes produced significant reactivation in peripheral tissues and blood AChE, but no significant reactivation of brain AChE. In another study, animals were pretreated i.m. with pyridostigmine 30 min prior to s.c. challenge with 2.0 x LD(50) of GB and treated i.m. 1 min later with atropine sulfate (2.0 mg/kg), plus a varied dose of oximes. MINA and DAM prevented or terminated GB-induced seizure activity and protected against GB lethality in a dose-dependent fashion. In contrast, none of the quaternary oximes prevented or stopped GB-induced seizures. Thus, tertiary oximes reactivated AChE in the brain, improved survival, and terminated seizures following GB intoxication.

The effects of monoisonitrosoacetone (MINA), diacetylmonoxime (DAM) and pyridine-2-aldoxime methiodide (P2AM) upon the cholinesterase of sarin poisoned rats have been studied. Monoisonitrosoacetone and diacetylmonoxime given before sarin protected blood and brain cholinesterase from inhibition. Monoisonitrosoacetone given after the appearance of signs of poisoning caused a rapid reactivation of brain cholinesterase. Diacetylmonoxime, at an equimolar dose, produced only a slight increase in enzyme activity, and pyridine-2-aldoxime methiodide, the best reactivator in vitro, reactivated blood but not brain cholinesterase. There is a relationship between protection and reactivation of brain cholinesterase and prevention and alleviation of signs of poisoning.

Three oximes, monoisonitrosoacetone (MINA), pyridine-2-aldoxime methiodide (PAM) and diacetylmonoxime (DAM), have been examined in combination with atropine as antidotes in sarin poisoning. When treatment was administered 15 min. before sarin, atropine enhanced the protective effect of MINA and DAM 2 to 3 times and of PAM 9 to 10 times in mice and rats. In mice, rats, and guinea-pigs, atropine increased by no more than 2 times the protective effect of all three oximes when given 30 sec. after sarin. Atropine given to monkeys 1 min. after sarin raised the LD50 approximately 3 times. When given in conjunction with MINA or DAM, the LD50 of sarin was raised 7 to 14 times.