The Protective Effect of Nimodipine, a Calcium Antagonist, and Its Influence on Soman Clearance in the Anaesthetized Rabbit

Abstract

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.

The Effect of the Calcium Antagonist Nimodipine on the Detoxification of Soman in Anaesthetized Rabbits

“…In an attempt to explain the mechanism underlying this protective effect, we studied the influence of nimodipine pre-treatment on the clearance of administered soman from the blood. We found that this pre-treatment considerably increased the rate of disappearance of soman (Karlsson et al 1994), presumably by reducing the peripheral vasoconstriction and thereby increasing the peripheral blood flow through the detoxifying organs. The disappearance of soman was so rapid in the Karlsson & Sellstrom (1986) study that the soman must have been hydrolysed or bound to the tissue during the first passage through the body.…”

Enzyme-Based Microassay for Accurate Determination of Soman in Blood Samples

“…3) could be obtained at a 10-fold lower concentration range of 0.01-1 nM. This is equivalent to a detectable concentration of 1.8 -18 pg/ml, which is comparable to that attained by high-resolution GC-MS (i.e., 3 pg/ml), clearly demonstrating the high level of sensitivity of the microassay technique (11).…”

Neurotoxicity of Organophosphates and Carbamates

“…Calcium channel blockers have also been studied in OP and CM poisoning (e.g., nimodipine) (Choudhary et al, 2002a;Dretchen et al, 1992;Karlsson et al, 1994).…”