Abstract
The effects of atropine and the oxime HI 6 on running performance, brain and plasma cholinesterase activity and brain catecholamines were investigated in mice intoxicated with sublethal doses of soman (100 μg/kg s.c.). The running time on a rotating mash wire drum (total running time 60 min) after injection of soman was reduced to 17.2 min. Treatment with atropine (10 mg/kg i.p.) or HI 6 (55 mg/kg i.p.) improved the running peformance to 48.2 and 44.8 min, respectively. Cholinesterase activity was decreased in soman poisoned mice to 47.3% in plasma and 43.5% in brain. Therapy with the oxime HI 6 resulted in a reactivation of soman-inhibited peripheral cholinesterase to 76.6%, but failed to reactivate central cholinesterase. Dopamine levels in mice brain were elevated in soman poisoning by 23.2%, whereas noradrenaline levels remained unchanged. The increase in brain dopamine levels was antagonized by atropine as well as by HI 6. The results of this study lead to the speculation that central dopaminergic mechanisms may be involved in soman toxicity as well as in the antidotal action of atropine and the mainly peripherally acting oxime HI 6.
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References
Anden NE, Wachtel H (1977) Increase in the turnover of brain dopamine by stimulation of muscarinic receptors outside the dopamine nerve terminals. J Pharm Pharmacol 29: 435–437
Arbogast H (1987) The effect of various compounds on the motor performance of mice impaired by phosphonofluoridic acid, methyl-1,2,2-trimethylpropyl ester (soman). Naunyn Schmiedeberg's Arch Pharmacol 335 (Suppl.) R 18
Clement JG (1981) Toxicology and pharmacology of bispyridinium oximes — insight into the mechanism of action vs soman poisoning in vivo. Fund Appl Toxicol 1: 193–202
Clement JG (1982) HI 6: Reactivation of central and peripheral acetylcholinesterase following inhibition by soman, sarin and tabun in vivo in the cat. Biochem Pharmacol 31: 1283–1287
Clement JG, Lockwood PA (1982) HI 6, an oxime which is an effective antidote of soman poisoning: A structure — activity study. Toxicol Appl Pharmacol 64: 140–146
Coudray-Lucas C, Prioux-Guyonneau M, Sentenac H, Cohen Y, Wepierre J (1983) Brain catecholamine metabolism changes and hypothermia in intoxication by anticholinesterase agents. Acta Pharmacol Toxicol 52: 224–229
Ellman GL, Courtney D, Andres V Jr, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholin esterase activity. Biochem Pharmacol 7: 88–95
French MC, Wetherell JR, White PDT (1983) The reversal by oximes and their deoximinomethyl analogues of neuromuscular block produced by soman. Eur J Pharmacol 91: 399–409
Glisson SN, Karczmar AG, Barnes L (1972) Cholinergic effects on adrenergic neurotransmitters in rabbit brain parts. Neuro-pharmacology 11: 465–477
Glisson SN, Karczmar AG, Barnes L (1974) Effects of diisopropylphosphonofluoridate on acetylcholine, cholinesterase and catecholamines of several parts of rabbit brain. Neuropharm-acology 13: 623–631
Irwin S (1968) Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacology 13: 222–257
Klimmek R, Eyer P (1986) Pharmacokinetics and pharmacodynamics of the oxime HI 6 in dogs. Arch Toxicol 59: 272–278
Lundy PM, Tremblay KP (1979) Ganglion blocking properties of some bispyridinium soman antagonists. Eur J Pharmacol 60: 47–53
Lundy PM, Shih TM (1983) Examination of the role of central cholinergic mechanisms in the therapeutic effects of HI 6 in organophosphate poisoning. J Neurochem 40: 1321–1328
Morgan WM, Pfeil KA (1979) Evidence for a cholinergic influence on catecholaminergic pathways terminating in the anterior and medial basal hypothalamus. Brain Res 173: 47–56
Nenner M (1970) Gleichzeitige Bestimmung der Aktivität von Acetylcholinesterase (EC 3.1.1.7.) in Vollblut, Plasma und Erythrozyten mit dem automatischen Titrator. Z Klin Chem Klin Biochem 8: 537–540
Oldiges H, Schöne K (1970) Pyridinium- und Imidazoliumsalzeals Antidote gegenüber Somanund Paraoxonvergiftungen bei Mäusen. Arch Toxicol 26: 293–305
Van Meter WG, Karczmar AG (1971) An effect of physostigmine on the central nervous system of rabbits, releated to brain levels of norepinephrine. Neuropharmacology 10: 379–390
Varagic V, Krstic M (1966) Adrenergic activation by anticholinesterases. Pharmacol Rev 18: 799–800
Westerink BNC (1983) Analysis of trace amounts of catecholamines and releated compounds in brain tissue: A study near the detection limit of liquid chromatography with electro chemical detection. J Liquid Chromatogr 6: 2337–2351
Wolthuis CL, Berends F, Meeter E (1984) Problems in the therapy of soman poisoning. Fundam Appl Toxicol 4: 183–192
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Reithmann, C., Arbogast, H., Hallek, M. et al. Studies on the role of central catecholaminergic mechanisms in the antidotal effect of the oxime HI 6 in soman poisoned mice. Arch Toxicol 62, 41–44 (1988). https://doi.org/10.1007/BF00316255
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DOI: https://doi.org/10.1007/BF00316255