Disease relevance of Trimedoxime

• Carbaryl-challenged mice also reflected a potentiation since TMB-4 exacerbated the toxicity more than 2-PAM Cl [1].
• On the other hand, trimedoxime seemed to be a significantly more efficacious reactivator than the others in the case of tabun poisonings [2].
• Effects of atropine, trimedoxime and methylprednisolone on the development of organophosphate-induced delayed polyneuropathy in the hen [3].
• Clinical signs and symptoms of OPIDP in the group which was treated with atropine (20 mg/kg, i.p.), TMB-4 (15 mg/kg, i.m.) and midazolam (2.5 mg/kg, i.m.) were more improved than that in the presence of a combination of atropine and TMB-4 [4].

Psychiatry related information on Trimedoxime

• Behavioral comparison of the oximes TMB-4, 2-PAM, and HI-6 in rats using operant conditioning [5].

High impact information on Trimedoxime

• The effects of the oximes 2-pyridine aldoxime methiodide (PAM), HI-6, HS-6, toxogonin and TMB-4 on the rate of carbamylation of membrane-bound bovine erythrocyte acetylcholinesterase were studied [6].
• The extent of hydrolysis of HI-6, MMB-4, and TMB-4 in 0.05 M, pH 7 phosphate buffer was approximately 50, 25, and less than 1%, respectively, after 20 d at room temperature [7].
• The efficacy of H oximes (HI-6, HLö-7), the oxime BI-6, and currently used oximes (pralidoxime, obidoxime, trimedoxime) to reactivate acetylcholinesterase inhibited by two nerve agents (tabun, VX agent) was tested in vitro [8].
• Tabun-inhibited AChE was completely reactivated by TMB-4, K027 and K048, with the overall reactivation rate constants of 306, 376 and 673 min(-1)M(-1), respectively [9].
• Influence of trimedoxime bromide on degradation of benactyzine in acidic injectable solutions [10].

Biological context of Trimedoxime

• Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons [11].

Associations of Trimedoxime with other chemical compounds

• In vitro potency of H oximes (HI-6, HLö-7), the oxime BI-6, and currently used oximes (pralidoxime, obidoxime, trimedoxime) to reactivate nerve agent-inhibited rat brain acetylcholinesterase [8].
• Based on 95% confidence limits the rank order of potentiation with eel AChE was TMB-4 = Toxogonin > HS-6 = HI-6 > 2-PAM Cl [1].
• When TMB-4 was added to the proscillaridin- and VX-inhibited AChE mixture, the inhibition decreased from 50% to 32% (a 0.37-fold decrease), whereas TMB-4 alone added to VX-inhibited AChE decreased the inhibition from 39% to 24% (a 0.38-fold decrease) [12].
• In our study, we have tested six acetylcholinesterase (AChE) reactivators (pralidoxime, obidoxime, HI-6, trimedoxime, BI-6 and Hlö-7) for reactivation of sarin- and cyclosarin-inhibited AChE using an in vitro reactivation test [13].
• When soman (2 X LD50) was given to TAB (an antidotal mixture of trimedoxime, atropine, and benactyzine ) pretreated rats, there was a greater than twofold reduction of glucose use in almost every brain region [14].

Gene context of Trimedoxime

• In essence, the substitution pattern influenced the inhibitory potency against AChE, where the most active bispyridiniumoxime (TMB-4) was bisbenzyl substituted followed by monobenzyl substituted, bismethyl substituted, and unsubstituted derivatives of TMB-4 [15].
• Mono- and bisbenzyloxime ethers of the bispyridinium derivative TMB-4 (UNO, DUO) are potent allosteric modulators of the muscarinic receptor attracting clinical interest in case of organophosphate poisoning [16].
• These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity [11].
• Various oximes (PAM, toxogonin, TMB-4, HS-6, HI-6, HGG-12, HGG-42) combined with atropine were compared as antidotes of soman, sarin and tabun poisoning in non-fasted CD-1 male mice [17].

References