Effect of Some Isocyclic,Aromatic,and Heterocyclic Compounds on Acetylcholine Synthesis. ∗

Abstract

In the presence of body fluids of patients with myasthenia gravis less acetylcholine is synthesized than in the presence of body fluids of healthy subjects.^1,2,3 In the following it was ascertained whether some isocyclic, aromatic hydrocarbons, and heterocyclic compounds modify the synthesis of acetylcholine. These substances were chosen because some of them occur in the animal organism as intermediate or end product of the metabolism, some are widely administered for their therapeutic effect, and some are known to modify the activity of various enzymes.

Experimental. The effect of the substances on the synthesis of acetylcholine was studied by the method described previously. 2 The amounts of acetylcholine synthesized are given in Table I. Isocyclic (cyclohexane, inositol) and aromatic hydrocarbons (benzol, toluol, benzoic acid, naphthalene) either did not modify the synthesis of acetylcholine or decreased it only in higher concentrations (10^-2 mols), Hydroxyl derivatives (phenol, p-aminophenol, hydroquinone, salicylic acid, α-naphthol, β-naphthol), aldehydes (benzaldehyde), and ketones (camphor, penicillin) decreased the synthesis in concentrations from 10^-5 mol. Conjugated products either did not modify the synthesis or decreased it slightly (potassium phenol sulfonate, phenacetine, diphenylamine, benzidine, acetylsalicylic acid, sulfonamides). From the heterocyclic compounds indol decreased the synthesis in concentrations from l0^-5 mol. Substitution in β position decreased this property of indol: skatol was somewhat less active depressor, indol-3-acetic acid was nearly inactive, dl-tryptophane was inactive, and l (—) tryptophane, the naturally occurring amino acid, increased the ability of frog brain to synthesize acetylcholine. Quinoline decreased the synthesis in concentrations from 10^-5 mol.; carbazole decreased it to a lesser degree.

Discussion. The substances used differ in their chemical structure and their ability to enter into various chemical reactions but are known to inactivate proteins. Therefore, it is possible that the decrease of acetylcholine synthesis was due to a partial inactivation of the protein component of the enzyme involved in the synthesis.