%0 Journal Article %A J. T. HOLDEN %A J. ROSSIER %A J. C. BEAUJOUAN %A P. GUYENET %A J. GLOWINSKI %T Inhibition of High-Affinity Choline Transport in Rat Striatal Synaptosomes by Alkyl Bisquaternary Ammonium Compounds %D 1975 %J Molecular Pharmacology %P 19-27 %V 11 %N 1 %X The high-affinity choline transport system in rat striatal synaptosomes was inhibited competitively by a series of long-chain alkyl bisquaternary ammonium compounds. BTE18 [octadecamethylenebis(triethylammonium bromide)] had a Ki value of 28 nM, and BHDM18 [octadecamethylenebis((2-hydroxyethyl)dimethylammonium bromide)] had a Ki value of 75 nM. BTE18 and hemicholinium-3 (HC-3) were equipotent competitive inhibitors. The transport of neither tryptophan nor dopamine was inhibited significantly by these compounds. Inhibitory activity increased as the alkyl chain length was increased, but reached a maximum at 17 or 18 methylene groups for bistriethyl- and bistrimethylammonium compounds. Triethylammonium compounds were more active than trimethylammonium compounds. Monoquaternary alkyltrimethylammonium compounds with 5-12 methylene groups were at least as active as the corresponding bis compounds. Various other choline-related analogues yielded the following findings. Hemicholinium-15 was much less active than HC-3. Troxonium and troxypyrrolium tosylate were moderately effective inhibitors, as was the cholinesterase inhibitor BW 284 C51. Long-chain alkyl bisquaternary ammonium compounds may be useful high-affinity analogues in studying the properties of this synaptosomal choline transport system. ACKNOWLEDGMENT The authors are indebted to Dr. Pierre Lefresne for his generous assistance and invaluable advice during this investigation. %U https://molpharm.aspetjournals.org/content/molpharm/11/1/19.full.pdf