Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos.

The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos > heptenophos > dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.

[The pharmacological correction of the immune homeostasis disorders in acute dichloroethane poisoning]. / Farmakologicheskaia korrektsiia narushenii immunnogo gomeostaza pri ostroi intoksikatsii dikhlorétanom.

Experiments on Wistar rats and noninbred mice showed that dipyroxim (10 mg/kg administered 3 times per 24 h) and thymogen (10 mg/kg daily for 3 days) restore the reduced under the effect of acute dichlorethane poisoning in a dose of 0.75 LD50 the organism's anti-infectious unspecific resistance and the main humoral and cell immune reactions. Summing of the effects of the drugs under study was encountered in the case of the T-dependent humoral immune response. The effect of dipyroxim was due to restoration of alpha-naphthyl-AS-acetatesterase of immunocytes and, possibly, other types of esterases of T-cells, macrophages, and monocytes.

Stability of trimedoxime in concentrated acidic injectable solutions.

The degradation of trimedoxime in concentrated (114 mg/ml) acidic solutions was studied at several temperatures in the pH range 3.0 to 4.3. The degradation profile showed a relationship indicative of first-order kinetics. Trimedoxime was found to be stable in the pH range 3.0 to 3.8, with maximum stability at pH 3.0. The activation energy of the hydrolysis reaction at pH 3.0 was found to be 19.4 kcal/mol, and the half-life was 124 years. General equations were derived relating the half-life of trimedoxime solution to pH and temperature. The t90 value at 25 degrees C was calculated for each pH value studied and was found to be 11 to 18 years within the pH range 3.0 to 3.8.