[2-Amino-2-thiazoline derivatives--a novel chemotype possessing muscarinomimetic effect]. / Proizvodnye 2-amino-2-tiazolina--novyi khemotip, obladaiushchii muskarinopodobnym deistviem.

Derivatives of 2-amino-2-thiazoline exhibit muscarinomimetic properties in model experiments with isolated rat ileum. The activity of compounds strongly depends on the nature of substituents in 5-position of thiazoline ring. The most active spasmogenic compound is 5-iodomethyl-2-amino-2-thiazoline hydroiodide (EC50 = 13 +/- 2 microM). Its effect is very similar to activity of cholinergic agent pilocarpine (EC50 = 14 +/- 4 microM), but "intrinsic activity" parameter a (alpha = 0.87 +/- 0.12) of 5-iodomethyl-2-amino-2-thiazoline was more significant. Ileum contractions induced by this compounds were inhibited by atropine. Derivatives of 2-amino-2-thiazoline (like pilocarpine) were not demonstrated nicotinomimetic properties. These compounds demonstrate very weak anti-AChE activity. For 5-iodomethyl-2-amino-2-thiazoline hydroiodide the IC50 value is 0.39 +/- 0.09 mM.

[The pharmacological selectivity of cholinesterase inhibitors is due to their antagonism with calcium ions]. / Farmakologicheskaia izbiratel'nost' ingibitorov kholinésteraz, obuslovlennaia ikh antagonizmom s ionami kal'tsiia.

The inhibitory activity of O-carbamoyl acylhydroxymoylchlorides was studied on the purified specimens of acetylcholinesterase from human erythrocytes and butirylcholinesterase from the horse blood serum. The pharmacological activity of these compounds was studied on isolated organs of rats. It was shown that introduction of N-aryl substituent in carbamate molecule increases the anticholinesterase activity and efficacy of blocking the neuromuscular conductivity. However it significantly diminishes the spasmogenic effect of N-arylcarbamates on the ileum. An increase in N-arylcarbamate concentration to 0.02-0.04 mM and higher results in a spasmolytic effect on the ileum which can be attributed to their "side" calcium blocking action.