engleski

Antidotal effect of adamantyl derivative Tamorf and carbamate Physostigmine in Soman intoxication

Acethylcholinesterase (AChE) is an extremely active enzyme. Irreversible inhibition of AChE by organophosphorus compounds (OPs) results in the accumulation of endogenous acetylcholine in synaptic cleft and paralysis of nerve impulse transmission in the central and peripheral nervous system. In order to find the best treatment of organophosphate poisoning new compounds have been synthesized and tested. The aim of this study was to evalute the pretreatment efficacy of adamantyl tenocyclidine derivative TAMORF which antagonize the NMDA receptors and might protect AChE. Its antidotal effect was compared with physostigmine which also has a good prophylactic efficacy in soman poisoning. The therapeutic efficacy of TAMORF and physostigmine was tested on rats poisoned with two different sub-lethal dose of soman (&frac14 ; ; and &frac12 ; ; of LD50). Our results indicate that TAMORF when administered 5 min before intoxication clearly stopped soman-induced seizures and markedly improved respiration of animals. In contrast to TAMORF, physostigmine seems to be slightly effective in the elimination of soman-induced toxicity in rats. Catalytic activities of AChE in brain, especially after administration of higher dose of soman (&frac12 ; ; of LD50) were additionally lower throughout of the experiment, except after 24 h. Similar results with physostigmine in contrast to TAMORF were obtained in plasma also. In conclusion, treatment with TAMORF seems to be a good alternative for current pretreatment in soman intoxication.

Adamantyl derivative; Physostigmine; Soman intoxication

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