Pharmacological inhibition of acetylcholine synthesis

Macintosh, F. C. ; Birks, R. I. ; Sastry, P. B. (1956) Pharmacological inhibition of acetylcholine synthesis Nature, 178 (1181). ISSN 0028-0836

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Schueler has designated as the "hemicholiniums" a series of quaternary bases which exhibit an unusual kind of toxicity. Chemically they are characterized by the incorporation of a choline (or choline-like) moiety into a six-membered ring through hemiacetal formation. Their most striking pharmacological action is respiratory paralysis: this is central in origin and late in onset, and when the dose is not too large can be prevented by the administration of either eserine or choline. Schueler noted that hemi-cholinium intoxication presents several features reminiscent of poisoning by botulinus or tetanus toxin, and suggested that it might be due to interference with some cholinergic mechanism. We thought that a substance having such effects might be a specific poison of acetylcholine synthesis, and through Dr. Schueler's kindness we have been able to verify this notion with compound No. 3 of his series, here called HC3.

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