Protection from lethality and behavioral incapacitation resulting from intoxication by soman (pinacolyl methylphosphonofluoridate) and treatment with atropine sulfate and 2-PAM chloride in the guinea pig, cavia porcellus.
The lethal and incapacitating effects of the toxic organophosphorus (OP) agent, soman were evaluated in guinea pigs. The protective effects of the standard therapies atropine sulfate (ATR) and pralidoxime chloride (2-PAM) in minimizing or reducing soman-produced lethality and incapacitation (evaluated using a modification of the rat conditioned avoidance procedure) were also studied. At 0.75 and 1.5 LD50 soman was extremely toxic and fast-acting; its effects appeared within five minutes, and its lethal effects occurred within the first three hours. Therapeutic combinations of ATR (64 or 128 mg/kg) and 2-PAM (25 or 100 mg/kg) protected animals from the lethality of soman, but not from its incapacitating effects. However, therapeutic treatment with ATR and 2-PAM also produced a behavioral toxicity in its own right, an effect which lasted for at least three hours in the guinea pig. This behavioral toxicity was lessened by reducing ATR dosage from 128 to 64 mg/kg, but 2-PAM dosage did not influence the behavioral toxicity of the treatment combinations within the range of dosages studied.
Romano
J A
JA
U.S. Army Medical Research Institute of Chemical Defense, Drug Assessment Division, Aberdeen Proving Ground, MD 21010-5425.
Terry
M R
MR
Murrow
M L
ML
Mays
M Z
MZ
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D011220:Pralidoxime Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D012999:Soman / Q000633:toxicity*
D002801:Cholinesterase Reactivators; D011220:Pralidoxime Compounds; D001285:Atropine; D012999:Soman; C028797:pralidoxime