Summary1. 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.
IntroductionSince the identification of acetylcholine as the natural cholinergic transmitter, a considerable amount of work has been done on the pharmacology, and enzymology, of this and related compounds, and also on other compounds having pharmacological actions similar to those of acetylcholine. These studies have been admirably summarized by Barlow (1964) and Triggle (1965). The major variations of the acetylcholine molecule which have been studied have involved modifications of the acyl and quaternary groups; few studies have been reported on the effects on pharmacological activity of altering the length of the choline chain. Hunt & Renshaw (1925) investigated the pharmacological activity of the acetoxymethyl trimethylammonium (I) and 3-acetoxypropyl trimethylammonium (II) ions, and showed that these compounds were less potent, as muscarinic agents, than acetyl-
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