1 The effect of pharmacological pretreatment (pyridos tigmine, benactyzine and trihexyphenidyle), desig nated Panpal, and antidotal treatment (the oxime HI- 6 plus benactyzine) in soman poisoning was investi gated in a rat model with on-line monitoring of respiratory and circulatory parameters.
2 Soman poisoning caused a high decrease in respiratory rate as well as minute respiratory volume and an increase in mean arterial pressure from 30-120 min following soman challenge. Soman at sublethal dose also significantly inhibited acetylcholinesterase activ ity in diaphragm and various brain parts.
3 Panpal pretreatment as well as antidotal treatment were effective in improving the respiratory and circulatory function disturbed by soman without the ability to increase significantly soman-inhibited acet ylcholinesterase activity in all brain parts studied.
4 The efficacy of combined Panpal pretreatment and antidotal treatment against sublethal soman poisoning was not different from the efficacy of Panpal pretreat ment or antidotal treatment alone.
5 The results of this investigation suggest that Panpal pretreatment as well as antidotal treatment are able to restore respiratory and circulatory function in soman- poisoned rats without significant reactivation of brain acetylcholinesterase.
Maynard RL, Beswick W.Organophosphorus compounds as chemical warfare agents. In Ballantyne B, Marrs TC (eds.) Clinical and Experimental Toxicology of Organophosphates and Carbamates. Butterworth - Heinemann , Oxford, England, 1992.
2.
Dawson RMReview of oximes available for the treatment of nerve agent poisoning . Journal of Applied Toxicology1994; 14: 317-331.
3.
Kassa J.Comparison of efficacy of two oximes (HI-6 and obidoxime) in soman poisoning in rats. Toxicology1995; 101: 167-174.
4.
Koplovitz I.Stewart JRA comparison of the efficacy of HI-6 and 2-PAM against soman, tabun, sarin and VX in the rabbit. Toxicology Letters1994; 70: 269-279.
5.
Shih T-M., Whalley ChE, Valdes JJA comparison of cholinergic effects of HI-6 and pralidoxime-2-chloride (2-PAM) in soman poisoning. Toxicology Letters1991 ; 55: 131-147.
6.
Shih T-M.Comparison of several oximes on reactivation of soman-induced blood, brain and tissue cholinesterase activity in rats. Archives of Toxicology1993; 67: 637-646.
7.
Marrs TCOrganophosphate poisoning. Pharmacology and Therapy1993; 58: 51-66.
8.
Chang EC et al. Neurophysiological concomitants of soman-induced respiratory depression in awake, behaving guinea pigs. Toxicology and Applied Pharmacology1990; 102: 233-250.
9.
Rickett DL, Glenn JF, Beers ETCentral respiratory effects versus neuromuscular actions of nerve agents. Neurotoxicology1986; 7: 225-236.
10.
Maksimovic M., Bregovec J., Deljac V., Binenfeld Z.Reactivation of organophosphate-inhibited cholinesterase by 4-cycloalkylcarbonyl-substituted bispyridinium monoximes . Archives of Toxicology1984; 55: 199-205.
11.
Wolthuis O., Berends F., Meeter E.Problems in the therapy of soman poisoning. Fundamental and Applied Toxicology1981; 1: 183-189.
12.
Rousseaux CG , Dua AKPharmacology of HI-6, an H series oxime. Canadian Journal of Physiology and Pharmacology1989; 67: 1183-1189.
13.
Kloog Y., Sokolovsky M.Bisquaternary pyridinium oximes as allosteric inhibitors of rat brain and muscarinic receptors. Molecular Pharmacology1985; 27: 418-428.
14.
Bajgar J., Fusek J., Vachek J.Theoretical approaches and practical possibilities of medical prophylaxis against nerve agent poisoning. CATE 95, May 2-6, 1995, Brno, Czech Republic.
15.
Brodbeck U., Gentinetta R.Inhibition of blood acetylcholinesterase after single and repeated doses of pyridostigmine. CBW Medical Treatment Symposium , December 5 - 8, 1994, Spiez, Switzerland.
16.
Worek F., Szinicz L.Cardiorespiratory function in nerve agent poisoned and oxime+atropine treated guinea pigs: effect of pyridostigmine pretreatment. Archives of Toxicology1995; 69: 322-329.
17.
Worek F., Kleine A., Szinicz L.Effect of pyridostigmine pretreatment on cardiorespiratory function in tabun poisoning. Human & Experimental Toxicology1995; 14: 634-642.
18.
Bajgar J., Fusek J., Vachek J.Treatment and prophylaxis against nerve agent poisoning. ASA Newsletter1994; 94-4: 10-11.
19.
Ellman GL, Courtney DK, Andres JrV., Featherstone FMA new and rapid colorimetric determination of acetylcholinesterase activity . Biochemistry and Pharmacology1961 ; 7: 88-95.
20.
Sachs L. (1992). Angewandte Statistik, Berlin : Springer, 1992.
21.
Kok A.REM sleep pathways and anticholinesterase intoxication: a mechanism for nerve agent-induced central respiratory failure. Medical Hypotheses1993; 41: 141-149.
22.
Brezenoff HE , McGee J., Knight V.The hypertensive response to soman and its relation to brain AChE inhibition. Acta Pharmacologica and Toxicologica1984; 55: 270-277.
23.
McCain WC, Wilcke J., Lee JC, Ehrich M.Effect of cyclic phenyl saligenin phosphate and paraoxon treatment on vascular response to adrenergic and cholinergic agents in hens. Journal of Toxicology and Environmental Health1995; 44: 167-187.
24.
van Helden Hpm, de Jonge J., Busker RW, Melchers BPTherapy of organophosphate poisoning in the rat by direct effects of oximes unrelated to ChE reactivation . Archives of Toxicology1991; 65: 586-593.
25.
Klimmek R., Eyer P.Pharmacokinetics and pharmacodynamics of the oxime HI6 in dogs. Archives of Toxicology1986; 59: 272-278.
26.
Worek F., Szinicz L.Investigation of acute cardiovascular and respiratory toxicity of HL67 dimethansulfonate and HI6 dichloride in anaesthetized guinea pigs. Pharmacology and Toxicology1993; 73: 91-95.
27.
Anderson DR , Harris LW, Woodard CL, Lennox WJThe effect of pyridostigmine pretreatment on oxime efficacy against intoxication by soman or VX in rats. Drug and Chemical Toxicology1992; 15: 285-294.
28.
Kassa J., Bajgar J.The influence of pharmacological pretreatment on efficacy of HI-6 oxime in combination with benactyzine in soman poisoning in rats. Human & Experimental Toxicology1996; 15: 383-388.
