STUDIES ON THE INTER-RELATIONSHIP OFCERTAIN CHOLINERGIC COMPOUNDS

I. The Pharmacology of 3-Acetoxy PhenyltrimethylammoniumMethylsulfate

¹ Department of Pharmacology, Cornell University Medical College, New York,New York

1. 3-Acetoxy phenyltrimethylammonium methylsulfate, Nu 2017, is astructural intermediate to acetylcholine and neostigmine. Its pharmacologic effects encompass both muscarinic and nicotinic properties although the latter predominate.

2. The duration of the effects of Nu 2017 in vivo is brief; this is in accord with its known susceptibility to esterasic hydrolysis.

3. The lethal effects of Nu 2017 are due entirely to a peripheral paralysis of respiration. Small doses of d-tubocurarine or brief positive pressure respiration prevent completely a lethal outcome but atropine is without influence on the duration or outcome of the poisoning. d-Tubocurarine, in addition, is aneffective antidote when given shortly after Nu 2017.

4. The effects of Nu 2017 on the blood pressure are qualitatively those of acetylcholine. Its effects on cardiac function are typically vagomimetic and,in addition, it exerts a positive inotropic action on the ventricle.

5. The most dramatic effect of Nu 2017 is its ability to antagonize a complete curarization. In fact, a mutual antagonism can be demonstrated between Nu 2017 and d-tubocurarine in the intact animal. This is of practical importancefor it implies that untoward effects from excessive amounts of Nu 2017 areunlikely in the presence of curare. Moreover, the safety of Nu 2017 as anantidote to curare is enhanced by its rapid elimination.

6. The effects of Nu 2017 on the smooth musculature of the blood vessels and gut, as well as on secretory structures, point up its relative impotence on these effectors in contrast to its potency on striated muscle.

7. The inter-relationship of Nu 2017 to acetyicholine, neostigmine, andanticholinesterases is discussed with reference to the influence of structure oncholinergic drug action. The potent direct effects of Nu 2017 and neostigmine on striated muscle are attributed to the basic Me₃N Phenyl grouping.

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