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.
soman; antidotal treatment; convulsion; prophylactic mixture; rat
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.