Abstract

A series of α-, β- and γ-substituted pyridylmethyltrimethylammonium salts (pyridylmethylTMA), which had previously been studied for synaptic blocking activity, have been reinvestigated in order to determine acetylcholine -like agonist activity on the cat superior cervical ganglion in vivo and the frog rectus abdominis in vitro. Benzyltrimethylammonium (BTMA) was included in order to assess the importance of the ring structure attached to the methyltrimethylammonium moiety in these tests. The results suggest that the three pyridyl compounds and BTMA can stimulate both nicotinic and muscarinic acetylcholine receptors in the ganglion. Such structural differences affect nicotine-like activity more than muscarine-like (i.e., pilocarpine-like) activity. The nicotine-like activity determined on the cat ganglion by retrograde i.a. external carotid artery injections before or after atropine i.v. in general paralleled that determined on the frog rectus. The rank order of these compounds was similar when muscarine-like activity was measured on the cat ganglion after nicotine and when it was determined in the cat by measurement of salivary secretion. Structure-activity relationships of these and related compounds are discussed and it is suggested that a survey of such substances under identical conditions of study might be profitable.