Pharmacology of some acetylcholine homologues

Abstract

1. The acetates of several long chain (3 to 12 methylene groups) analogues of choline have been prepared and their pharmacological properties studied.2. None of the compounds had a high level of activity at the post-ganglionic parasympathetic acetylcholine receptors. The lower members of the series showed weak agonist activity and the homologues with 8 to 10 methylene groups had very weak anticholinergic activity.3. All the compounds had a depolarizing action at the acetylcholine receptors of the neuromuscular junction and of sympathetic ganglia. At the neuromuscular junction there were two peaks of stimulant activity, one with the hexamethylene and one with the dodecamethylene homologue, whereas at the ganglion there was only one peak, with the hexamethylene homologue.4. The ganglion-stimulant activity of the higher members of the series was blocked by pretreatment with the anticholinesterase drug dyflos, whereas the activity of lower members was either unaffected by such treatment or slightly potentiated.5. The results are discussed in terms of possible spatial arrangements of acetylcholine receptor units in the neuromuscular junction and the ganglion.