The protective effect of nimodipine, a calcium antagonist, and its influence on soman clearance in the anaesthetized rabbit.
The effect of pretreatment with a vasoactive compound, nimodipine, on soman intoxication in peripheral organs of rabbits was studied by measuring changes in the cholinesterase and acetylcholinesterase activity and by measuring clearance of soman in blood using gas chromatography/high resolution mass spectrometry. In animals receiving soman only, initial blood concentrations were approximately 100 ng mL-1 and were still detectable after 5 min. The clearance rate of soman in blood markedly increased following nimodipine pretreatment such that soman was below the detection limit (0.002-0.003 ng mL-1) in all samples. Soman injection caused a significant inhibition of the acetylcholinesterase activity in serum, and in brain. In rabbits pretreated with nimodipine, no significant inhibition of acetylcholinesterase activity occurred after soman injection. In view of the effects of nimodipine on soman clearance and on the acetylcholinesterase and cholinesterase inhibition during soman intoxication, we suggest that nimodipine has profound circulatory effects, which during soman intoxication, increase the vascular perfusion through the body and thereby increase the detoxifying capacity.
Karlsson
B
B
National Defence Research Establishment, Department of NBC Defence, Umeã, Sweden.
Fredriksson
S A
SA
Sellström
A
A
Algers
G
G
D000110:Acetylcholinesterase / Q000032:analysis; D000758:Anesthesia; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002802:Cholinesterases / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D007274:Injections, Intraperitoneal; D009553:Nimodipine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011041:Poisoning / Q000188:drug therapy*; D011817:Rabbits; D012999:Soman / Q000097:blood* / Q000633:toxicity*; D014018:Tissue Distribution
D009553:Nimodipine; D012999:Soman; D000110:Acetylcholinesterase; D002802:Cholinesterases; D002118:Calcium