The Antagonistic Action of Choline and its Triethyl Analogue. ∗

Abstract

In recent years, considerable interest has been developed in the interference with biological processes through the use of analogues of essential metabolites.

Triethyl choline chloride, the ethyl analogue of choline, is an interesting compound from this point of view. Triethyl choline is not capable of replacing choline in biological processes in which choline acts as a methyl donor, 1 but its lipotropic activity has been found to be substantially equal to that of choline itself. 2 Since the formation of acetyl choline presumably would not involve transmethylation directly, the triethyl derivative might possibly be handled similarly to choline in the systems involving its acetylation. The acetyl derivative of triethyl choline, however, does not have any of the stimulating actions of acetyl choline. A competition with choline in these systems should therefore lead to diminished formation of active acetyl derivatives.

Triethyl choline chloride, when injected into animals in sufficient amounts, is acutely toxic. 3 The symptoms demonstrated include apparent muscular weakness, apparent exophthalmos, and convulsions, followed by death within a few minutes. On the assumption that this acute toxicity is due to competition with choline in an essential biological system, choline was administered to see whether it would protect animals against its triethyl analogue.

Forty-four mice, ranging in weight from 16 to 23 g, were divided into 2 groups containing animals of corresponding weights. The mice of one group were injected in the hind leg with triethyl choline chloride, prepared according to the directions of Channon and Smith. 4 Six out of 9 mice given 1.25 mg died. Twelve out of 13 mice given 1.75 mg died.

The mice of the other group were treated with the same amounts of triethyl choline chloride and an equal weight of choline chloride. Out of 9 mice given 1.25 mg triethyl choline chloride together with 1.25 mg choline chloride, all survived. Out of 13 mice given 1.75 mg triethyl choline chloride together with 1.75 mg choline chloride, 12 survived.