The effectiveness of Parpanit in the treatment of organophosphorus poisoning was examined and compared with that of atropine sulfate. The potency of Parpanit was assessed in the mouse, rat, hamster, guinea pig, and rabbit against sarin, tabun, soman, CMPF, and DSDP in treatments in which the oximes P2S and TMB4 were used both singly and together. The effectiveness of the treatments utilizing both cholinolytics varied with the species used for assay, with the oxime used in combination, and with the nature and level of challenge of the organophosphorus inhibitors. The mean activity of Parpanit relative to atropine taken from a total of 102 trials indicated it to be 4.2 times as effective, with the potency ratio varying from 0.17 to 100 depending on the specific test. The acute oral toxicity of Parpanit in weanling rats was 2.9 g/kg (2.4–3.4). In a chronic toxicity study where daily oral doses as high as 1/5 LD50 were applied for 30 days, no evidence of accumulative effects could be found nor was there any evidence that the protective capacity of Parpanit against sarin was affected by the extended application of the drug.
The selection, for use in combatting organophosphorus poisoning, of five binary cholinolytic drug combinations from previously screened compounds is described. Their effectiveness was determined in mouse, rat, guinea pig, hamster, and rabbit against TEPP, DFP, Paraoxon, sarin, tabun, O,O-diethyl S-2-diethyl-aminoethyl phosphorothiolate (DSDP), and cyclohexyl methylphosphonofluoridate (CMPF) in treatments in which the oximes P2S and TMB4 were used both singly and together. The effectiveness of each cholinolytic combination was compared with that of atropine sulfate on the basis of nine quantitative tests and one qualitative test.The following combinations had highest and almost equal effectiveness: G3063, a Caramiphen hydrochloride (Parpanit®) analogue, with triflupromazine; and Win 5779-6, a benzilate type ester, with triflupromazine. The combinations of Win 5779-6 with Parpanit®, atropine methylbromide with Parpanit®, and G3063 with G5130, another Parpanit® analogue, were second in activity and almost equal in potency. Atropine sulfate was the least effective. The most effective oximes were TMB4, and a lower dose mixture of P2S plus TMB4, which were found almost equal in potency but superior in effectiveness to P2S alone.
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