Cholinolytics in the Treatment of Anticholinesterase Poisoning: Iv. The Effectiveness of Five Binary Combinations of Cholinolytics With Oximes in the Treatment of Organophosphorus Poisoning

Abstract

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.

Preparation of antidotes for anticholinesterase poisoning. IV. Synthesis and protective effectiveness of 2′-(cis- and trans-2″-hydroxycyclohexyl)aminoethyl 1-phenylcyclopentanecarboxylate hydrochlorides

“…In connection with our continuing studies on the effectiveness of Parpanit (2'-diethylaminoethyl 1-phei~ylcyclopentanecarboxylate hydrochloride) and its analogues as substitutes for, or adjuncts to, atropine in the treatment of rodents which have been poisoned with organophosphorus anticholinesterases (1)(2)(3)(4)(5) it was desired to examine compounds containing a hydroxyl group close to and in known stereochemical relationship with the amino group in Parpanit. To this end the synthesis of compounds of the type 1 and 2 (R = C,H, or H) has been briefly examined and the in vivo protective effectiveness of compounds 1 and 2 (R = H) was determined.…”