Abstract
The LD50 of GB (sarin) given intravenously was increased more than 100-fold when rabbits were treated intravenously with atropine and 10 mg/kg of a 1:1 mixture of the monoquaternary oxime, 2-PAMCl, and a bisquaternary oxime, TMB4Cl2. A similar dose of TMB4 alone also antagonized this high dose of GB, but failed to save all animals at lower doses of GB. Atropine alone or the mixed oximes alone provided only minimal therapeutic effects against GB. In dogs under similar conditions, either a single oxime, 2-PAMCl, or the mixed oximes, 2-PAMCl + TMB4Cl2, 1:1, with atropine, saved all dogs given 70 times the LD50 of GB, but only the mixed oximes were highly effective against 70 times the LD50 of GA (tabun).
When similar doses of oximes with atropine were given to rabbits prophylactically, by mouth or intramuscularly, 30 minutes before subcutaneous GB, survival occurred only after much smaller GB doses than those wherein oximeatropine therapy was given soon after GB.
Tolerance for GB in cats was not a function of time for recovery of muscle function.
In rabbits and mice, the bisquaternary oximes were more acutely toxic by the intravenous route than the monoquaternary type. A 1:1 mixture of the two was intermediate in toxicity.
Of the oximes studied, the 1:1 mixture of the chloride salts of the mono- and bisquaternary types was most suitable for therapeutic purposes, because of its effectiveness against GB and GA, smaller acute toxicity, and greater solubility and stability of the salt form.
Footnotes
- Received September 14, 1960.
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