Studies on the role of central catecholaminergic mechanisms in the antidotal effect of the oxime HI 6 in soman poisoned mice.

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 micrograms/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 performance 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.