The inhibition and protection of cholinesterase by physostigmine and pyridostigmine against soman poisoning in vivo

Abstract

It has been shown that some reversible cholinesterase (ChE) inhibitors as physostigmine and pyridostigmine are prophylactically effective in organophosphate poisoning. The inhibition and protection of ChE against Soman poisoning with the above mentioned drugs was investigated in mice. (1) Physostigmine and pyridostigmine significantly inhibited the ChE in whole blood in vivo and their inhibitory potencies with equitoxic doses were approximately equal (1/5 LD 50 about 30%; 1/2 LD 50 about 45% respectively). Physostigmine also significantly inhibited brain ChE and its potency was slightly weaker than that in blood; but pyridostigmine only slightly inhibited brain ChE (17%) with large dose (1/2 LD 50). The extent of inhibition was in parallel with the dosage of the drugs used. (2) Physostigmine had definite protection in the blood and brain ChE against Soman poisoning. The extent of protection was in parallel with the dosage used. The protection of blood ChE by pyridostigmine was weaker than that by physostigmine. There was no protection of brain ChE by pyridostigmine. (3) The inhibitory potency of equitoxic doses of physostigmine and pyridostigmine in the ChE of diaphragm muscle was equal too (1/2 LD 50 about 45%), and the protective effect of physostigmine was still greater than that of pyridostigmine in Soman poisoning. (4) The time course of blood ChE inhibition by physostigmine in vivo was of short duration. While 30 minutes after administration of physostigmine, the ChE activity gradually recovered and it returned to normal level after 4 hours. The blood ChE inhibition by pyridostigmine reached a peak level after 2 hours, and the ChE activity slowly increased after 4 hours, but there was 30% of ChE activity still inhibited after 8 hours. Physostigmine and pyridostigmine, the reversible ChE inhibitors with carbamate structure, have definite ChE protection against Soman poisoning. The prophylactic efficacy was obviously correlated with their ChE protective potency. Evaluating physostigmine and pyridostigmine based on their efficacy, toxicity, adverse effects, duration, availability and stability, we recommend that pyridostigmine is the drug of choice in the prophylaxis against nerve gas poisoning.