AUTONOMIC BLOCKING COMPOUNDS. III. THE GANGLION BLOCKING AND PARASYMPATHOLYTIC ACTIONS OF A SERIES OF QUATERNARY AMMONIUM DERIVATIVES CONTAINING THE PHENOTHIAZINE NUCLEUS

¹ Division of Biological Research, G. D. Searle & Co., Chicago 80, Illinois

The ganglion blocking and parasympatholytic actions of a series of quaternary ammonium derivatives of phenothiazine (PTZ) was studied. Almost all of the compounds produced ganglionic blockade; the most potent compound, 10-[2-(2,5-dimethyl-1-pyrollidinyl)ethyl] phenothiazine methobromide was three and one-half times as active as tetraethylammonium on a molar basis.

Compounds with greatest parasympatholytic activity have a two carbon alkylene chain linking the quaternary nitrogen to the PTZ nucleus. Introduction of a methyl side chain on the alkylene carbon adjacent (alpha) to the quaternary nitrogen improved both types of blocking action. However, introduction of a methylene, ethylene, carbonyl, carbonyloxy or amido group between the alkamine and the 10 position of the PTZ nucleus markedly decreased the parasympatholytic potency.

The nature of the N-alkyl groups had a significant influence on the parasympatholytic activity. Ethyl was superior to methyl but hydroxyethyl was inferior. The compound having the greatest activity was 10-[2-(1-diethylaminopropyl)] phenothiazine methochloride.