Disease relevance of 4-(nitrosomethylidene)-1-[[4-(nitrosomethylidene)pyridin-1-yl]methoxymethyl]pyridine

• Neither HI-6 nor toxogonin antagonized oxotremorine-induced hypothermia, indicating that these oximes do not possess central cholinolytic activity [1].
• After passing toxicity and experimental therapeutic tests, four oxime cholinesterase reactivators [PAM (pyridine aldoxime methiodide), PAC (pralidoxime, pyridine aldoxime methylchloride), TMB4 (trimedoxime), and DMO4 (obidoxime, Toxogonin, LüH6)] were compared in clinical trials [2].
• Intraperitoneal (i.p.) injection of HI-6 or Toxogonin (50 mg/kg), immediately after 10 min inhalation exposure to soman, also significantly improved the ex vivo cholinergic contraction response of the trachea (decapitation 15 min after oxime administration) [3].

High impact information on 4-(nitrosomethylidene)-1-[[4-(nitrosomethylidene)pyridin-1-yl]methoxymethyl]pyridine

• The in vitro reactivation potency of the alpha-keto thiohydroximates approaches and even surpasses that of 2-PAM and toxogonin for GD-inhibited AChE [4].
• The potassium (51 mM) evoked release of [(3)H]-acetylcholine and the liberation of [(3)H]-choline were determined in hippocampal slices following in vitro exposure to soman and five oximes (toxogonin, HI-6, HLö-7, P2S and 2-PAM) in separate experiments by superfusion [5].
• Only limited reactivation of the acetylcholinesterase activity was observed in superfusion experiments with toxogonin, HI-6, P2S and 2-PAM following exposure of hippocampal slices to soman [5].
• In vitro effects of toxogonin, HI-6 and HLö-7 on the release of [3H]acetylcholine from peripheral cholinergic nerves in rat airway smooth muscle [6].
• HI-6, but neither toxogonin nor PAM Cl, antagonized sarin-induced hypothermia and reactivated brain acetylcholinesterase, in particular hypothalamic acetylcholinesterase [1].

Chemical compound and disease context of 4-(nitrosomethylidene)-1-[[4-(nitrosomethylidene)pyridin-1-yl]methoxymethyl]pyridine

• The toxicity of the carbamate insecticide carbaryl, however, was significantly increased by toxogonin [7].

Biological context of 4-(nitrosomethylidene)-1-[[4-(nitrosomethylidene)pyridin-1-yl]methoxymethyl]pyridine

• However, when toxogonin was substituted for HI-6 in the therapeutic mixture, all three animals poisoned with 5 x LD50 of soman died [8].
• The side effects of four phosphorylated cholinesterase reactivators (oximes): contrathion, TMB4, toxogonine and 1574 SEBC on membrane properties and synaptic transmission of Aplysia central neurons were investigated [9].

Anatomical context of 4-(nitrosomethylidene)-1-[[4-(nitrosomethylidene)pyridin-1-yl]methoxymethyl]pyridine

• The acetylcholinesterase activity in erythrocytes, cerebrum and diaphragm of surviving mice 20 hours after organophosphate intoxication was similar both in toxogonin and P2S treated animals and untreated animals [7].

Associations of 4-(nitrosomethylidene)-1-[[4-(nitrosomethylidene)pyridin-1-yl]methoxymethyl]pyridine with other chemical compounds

• Effect of pyridostigmine pretreatment, HI-6 and Toxogonin treatment on rat tracheal smooth muscle response to cholinergic stimulation after organophosphorus inhalation exposure [3].

References