CHOLINOLYTICS IN THE TREATMENT OF ANTICHOLINESTERASE POISONING: I. THE EFFECTIVENESS OF CERTAIN CHOLINOLYTICS IN COMBINATION WITH AN OXIME FOR TREATMENT OF SARIN POISONING

Abstract

The protection to sarin poisoning afforded mice by treatment with N-methylpyridinium-2-aldoxime methanesulphonate (P-2-S) in combination with each of 34 cholinolytic compounds used as substitutes for atropine sulphate has been assessed. Twenty-two of the drugs examined in the mouse at a dosage of 50 μmoles/kg gave protection equal to or greater than that afforded by atropine sulphate. The most potent drug was 4′-N-methylpiperidyl 1-phenylcyclopen-tanecarboxylate hydrochloride (G-3063), which was 2.3-fold as effective as atropine sulphate.l-2′-Diethylaminoethyl α-cyclohexyl-α-2″-thienyl glycolate d-bitartrate (Win 5779-6),2′ -diethylaminoethyl 1-phenylcyclopentanecarboxylate hydrochloride (Parpanit), and l-tropyl α-methyltropate hydrochloride were 1.8-, 1.5-, and 1.4-fold as effective, respectively. Eighteen of the compounds were examined in the rat, with 11 showing potency equal to or greater than that shown by atropine sulphate. In this species the most potent drugs were G-3063, which had 4.0 times the activity of atropine sulphate, Win 5779–6 (4.8-fold), and atropine methanesulphonate, followed by 1-cyclohexyl-1-(2′-thienyl)-3-(1″-piperidyl)-propanol-1 hydrochloride (Win 12085) and Parpanit.