Naslov
Evaluation of Antidotal Effects of Adamantyl Derivative Tamorf in Soman Poisoning

Autori
Lucić Vrdoljak, Ana ; Radić, Božica ; Garaj-Vrhovac, Vera ; Kopjar, Nevenka ; Žlender, Vilim

Izvornik
Journal of Applied Toxicology (0260-437X) 26 (2006); 56-63

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
adamantanes; soman; brain acetylcholinesterase activity; N-methyl-D-aspartete (NMDA) receptors; genotoxic effects; comet assay

Sažetak
Acetylcholinesterase (AChE ; EC 3.1.1.7), causes an array of toxic effects in the central nervous system. Adamanyl tenocyclidine derivative Tamorf (1-[2-(2-thienyl)-2-adamantyl] morpholine), a compound with potential activity at the N-methyl-D-aspartate (NMDA) receptors and with neuroprotective properties, is effective against convulsions and brain lesions related to soman poisoning. The objective of this study was to evaluate the antidotal potency of Tamorf (2.5 mg/kg), which was tested alone as a pre-treatment or in combination with atropine (10.0 mg/kg) as a therapy in rats poisoned with two different sub-lethal doses of soman (&frac14 ; and &frac12 ; of LD50). The effect of Tamorf was compared with carbamate physostigmine (0.1 mg/kg). The study also determined possible genotoxic effects of Tamorf and physostigmine, especially primary DNA damage in white blood cells, liver and brain tissue. Tamorf administered five minutes before poisoning stopped soman-induced seizures, was successful against sub-lethal doses of soman and protected AChE activity in the brain (P=0.0014, P=0.0019), and in plasma (P=0.0464, P=0.0405). Compared to Tamorf, physostigmine was slightly effective in the elimination of soman-induced poisoning in rats. The pharmacological effect of Tamorf and atropine was less effective as therapy, but did not increase soman toxicity (P>0.05 for all interactions). The obtained results indicate that Tamorf and physostigmine are not genotoxic to rats in concentrations tested. Treatment with Tamorf seems to be a good alternative for current pretreatment in soman poisoning. Its antidotal mechanism is complex and is based on combined biochemical and receptor properties.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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