SUMMARY
The protective and anticonvulsive efficacy of two prophylactic mixtures (PANPAL consisting of
pyridostigmine, benactyzine, and trihexyphenidyle and pyridostigmine plus biperiden) administered
prior to the administration of soman in a lethal dose (1.5 LD50) with or without antidotal treatment
(atropine + HI-6) was evaluated using rats as experimental animals. The pretreatment was applied
30 and 60 min before intoxication and the antidotal therapy was administered 1 min after soman
poisoning. The anticonvulsive efficacy of both prophylactic combinations was determined using a
seven degree scale. Non-treated soman-poisoned rats died within 10 min after soman challenge
showing severe tremor, subconvulsions and generalized convulsions. More than 90% of pretreated
animals survived for 24 hrs following soman poisoning and they were observed to be free from
soman-induced toxic signs 24 hrs after soman administration. Our findings confirm that both
prophylactic mixtures are able not only to protect experimental animals from the lethal effects of
soman but also to eliminate most soman-induced toxic signs. Our results confirm that both
prophylactic mixtures should be considered as a pretreatment for nerve agent poisoning, especially
in the case of the threat of exposure to soman.
KEY WORDS
soman; antidotal treatment; convulsion; prophylactic mixture; rat
REFERENCES
Anderson DR, Harris LW, Woodard CL,
Lennox WI: The effect of pyridostigmine
pretreatment on oxime efficacy against
intoxication by soman or VX in rats. Drug
Chem Toxicol 15:285-294, 1992.
Bajgar J: Present view on toxidynamics of soman
poisoning. Acta Med (Hradec Kralove) 39:101-105, 1996.
Bajgar J, Fusek J, Vachek J: Treatment and
prophylaxis against nerve agent poisoning. ASA
Newslett 94 (no 4):10-17, 1994.
Kassa J: Comparison of efficacy of two oximes
(HI-6 and obidoxime) in soman poisoning in
rats. Toxicology 101:167-174, 1995.
Kassa J: Review of oximes in the antidotal
treatment of poisoning by organophosphorus
nerve agents. J Toxicol Clin Toxicol 40:803-816, 2002.
Kassa J, Bajgar J: The influence of
pharmacological pretreatment on efficacy of
HI-6 oxime in combination with benactyzine in
soman poisoning in rats. Hum Exp Toxicol 15:383-388, 1996.
Kassa J, Fusek J: The positive influence of
a cholinergic-anticholinergic pretreatment and
antidotal treatment on rats poisoned with
supralethal doses of soman. Toxicology 128:1-7, 1998.
Kassa J, Krejcova G, Samnaliev I: A comparison
of the neuroprotective efficacy of
pharmacological pretreatment and antidotal
treatment in soman-poisoned rats. Acta Med
(Hradec Kralove) 46:101-107, 2003.
Kassa J, Vachek J: A comparison of the
efficacy of pyridostigmine alone and the
combination of pyridostigmine with
anticholinergic drugs as pharmacological
pretreatment of tabun-poisoned rats and mice.
Toxicology 177:179-185, 2002.
Kassa J, Vachek J, Bajgar J, Fusek J:
A combination of pyridostigmine with
anticholinergic drugs: effective pharmacological
pretreatment of soman-poisoned mice. ASA
Newslett 84:16-19, 2001a.
Kassa J, Vachek J, Bajgar J, Fusek J:
A comparison of the efficacy of pharmacological
pretreatments against soman in mice. Voj Zdrav
Listy, Suppl. 1, 70:22-25, 2001b.
Lallement G, Clarenson D, Brochier G,
Baubichon D, Golonnier M, Blanchet G,
Mestriers JC: Efficacy of atropine/pralidoxime/
diazepam or atropine/HI-6/prodiazepam in
primates intoxicated by soman. Pharmacol
Biochem Behav 56:325-332, 1997.
Marrs T: Organophosphate poisoning. Pharmacol
Therap 58:51-66, 1993.
McDonough J, Shih T-M: Neuro
pharmacological mechanisms of nerve agents-induced
seizures and neuropathology. Neurosci
Biobehav Rev 21:559-579, 1997.
McLeod CG, Singer W, Harrington DG: Acute
neuropathology in soman poisoned rats. Fundam
Appl Toxicol 5:53-58, 1984.
Petras JM: Soman neurotoxicity. Fundam Appl
Toxicol 1:73-83, 1983.
Samnaliev I: Efficacy of biperiden and HI-6 as
prophylactic combination against convulsions
produced by highly toxic organophosphorus
compounds. Voj Zdrav Listy, Suppl. 1, 70:30-32, 2001.
Samnaliev I: Assessment of the drug combination
containing biperiden and cholinesterase
reactivators as a prophylaxis against soman
induced poisoning. Voj zdrav Listy 71:86-92,2002.
Shih T-M: Comparison of several oximes on
reactivation of soman-induced blood, brain and
tissue cholinesterase activity in rats. Arch
Toxicol 7:637-646, 1993.
Vachek J, Kassa J, Fusek J, Bajgar J: Present
possibilities of treatment of organophosphate
poisoning (In Czech). Sbor Ved Praci VLA JEP
Hradec Kralove 116:67-96, 1993.
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