Cholinolytics in the Treatment of Anticholinesterase Poisoning: Iii. The Effects of Quaternization and Alteration of Anionic Function on the Potency of Cholinolytics in the Treatment of Sarin Poisoning

Abstract

Twenty-one quaternary ammonium salts of cholinolytic drugs have been assessed for potency against Sarin poisoning in mice and rats in a treatment using N-methylpyridinium-2-aldoxime methanesulphonate (P-2-S) as a reactivating oxime. Compounds examined included the methylbromides of six cholinolytics of known effectiveness and eight N-alkylbromides of Parpanit. An attempt was also made to assess the effect of different anions in both tertiary and quaternary salts of atropine and Parpanit.None of the quaternary salts exceeded the potency of atropine sulphate by a factor greater than 1.5 in trials with rats when the compounds were examined in combination with P-2-S, although similar tests in mice showed Trasentin methylbromide and Parpanit n-propylbromide to be more than 1.5 times as active as atropine sulphate. In trials where the compounds were used in conjunction with atropine sulphate and P-2-S, 10 raised the activity of atropine in mice by a factor exceeding 1.5, with the highest value (3.6) being obtained with Parpanit methylmethanesulphonate while in the rat trials 16 quaternaries were effective, the greatest increase (7.5-fold) being obtained with Parpanit benzylbromide.No conclusion on the relative effectiveness of quaternary salts versus their tertiary counterparts could be reached since protective capacity of the quaternary salts altered with the species used, the nature of the test, the cholinolytic, the type of alkyl group introduced, and, at least in the case of Parpanit, depended upon the nature of the anionic group present.