ON THE PHARMACOLOGIC ACTION OF SOME NEW CHOLINE DERIVATIVES IN RELATION TO THEIR CHEMICAL CONSTITUTION

¹ From the Department of Pharmacology, School of Medicine, Western Reserve University, Cleveland, Ohio

The pharmacologic properties of the following choline derivatives were studied: Trimethyl-ethyl-ammonium-dichloride, trimethyl-ammonium-ethylamine-chloride, trimethyl-ammonium-ethyl-methylamine-chloride, and di-(trimethyl-ammonium)-ethyl-dichloride.

In doses of 2 mgm. per gram of frog they all produce depression of the central nervous system, first of the medulla later also of the higher centers.

Choline dichloride and di-(trimethyl-ammonium)-ethyl-dichloride have curare action, paralysing the motor receptive mechanism of the striated muscle. With the two amines this effect is overshadowed by the depressant effect on the muscle itself.

All compounds are parasympathetic stimulants causing salivation, bronchospasm, intestinal stimulation and slowing of the heart.

Like choline, choline dichloride and di-trimethyl-ammonium-ethyl-dichloride produce only rise of the blood pressure after the administration of atropine; trimethyl-ammonium-ethyl-amine-chloride shows still some primary fall.

The secondary rise of the blood pressure is abolished by premedication with nicotine with all compounds.

Substitution of the alcoholic hydroxy group by chlorine and the quaternary radicle

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reinforces only the pharmacologic action characteristic for choline, without introducing any new modification.

Substitution by an amino or methylamino group seems to reinforce the depressant action on the muscular tissue.

From this it appears that the

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nucleus is the essential part of the choline molecule in regard to its pharmacologic action.