RELATIONSHIP BETWEEN PERIPHERAL CHOLINOLYTIC POTENCY AND TETRAETHYLPYROPHOSPHATE ANTAGONISM OF A SERIES OF ATROPINE SUBSTITUTES

¹ Pharmacology Section, Sterling-Winthrop Research Institute, Rensselaer, New York

Thirty-five alkanol substituted amines, substituted acetic acid esters, substituted tropanes and - and -substituted acetic acid esters were tested for their antagonism of tetraethylpyrophosphate (TEPP) toxicity in mice. TEPP antagonism was tested either in the presence of Mytolon or of Mytolon and atropine methylnitrate (Eumydrine). Mouse mydriasis was used to evaluate the peripheral cholinolytic potency of these compounds.

Eumydrine alone or Eumydrine with Mytolon provides only minimal protection against TEPP toxicity. Eumydrine does not increase the protective action of the cholinolytic compounds studied.

The structural changes that increase the peripheral cholinolytic potency also increase the anti-TEPP action of the compounds tested. A close correlation was found between the anti-TEPP and peripheral cholinolytic actions of the 34 compounds tested.

The suggestion is offered that both TEPP toxicity and protection afforded by atropine-like agents is, in mice, central in nature, and that the statistical correlation demonstrated supplies additional evidence for the hypothesis that cholinergic transmission is involved in these phenomena.