73. Chronic toxicity of calciumdisodium ethylenediamine tetraacetate

Abstract

The incorporation of choline by isolated synaptosomes and synaptic vesicles from guinea pig cortices was inhibited by a variety of quaternary ammonium compounds. Two preparations of synaptosomes (P2 and B) and one of synaptic vesicles (D) were used and in most instances little quantitative difference was found in the inhibition of choline uptake between the fractions. Hemicholinium (HC-3) and triethylcholine (TEC) inhibited choline uptake at high concentrations, whereas at 10−5 M, both TEC and HC-3 potentiated the uptake of choline into synaptosomal fractions. A number of drugs which influence cholinergic transmission inhibited choline uptake by a competitive mechanism. Decamethonium (C10) was found to inhibit choline uptake more than hexamethonium (C6). Tetramethylammonium and tetraethylammonium affected choline uptake to a similar extent. d-Tubocurarine was an inhibitor of choline uptake, and physostigmine, a tertiary compound, also inhibited choline uptake. Atropine, methacholine and acetylcholine inhibited choline uptake but carbachol had almost no effect.A number of drugs which influence brain acetylcholine levels—picrotoxin, leptazol, d-amphetamine, pentobarbitone, and morphine—had no effect on choline uptake at concentrations of 2× 10−1 M. A hydroxyethyl group did not increase inhibitory activity, because the decamethylene bis(hydroxyethyl)dimethylammonium (C10-dicholine) salt was as active as C10. The hexamethylene compound (C6-dicholine) was less active than C10-dicholine but was as active as C6. From C3- to C5-dicholine, a shortening of the interquaternary nitrogen distance increased the inhibitory activity of the compounds for choline uptake.