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.

Sub-lethal doses of nicotine have been shown to protect mice from the lethal effects of subsequently administered doses of the same drug. The evidence suggests that a metabolic product of nicotine is responsible for the protective action. In an attempt to identify this metabolite it was shown that cotinine had no protective action but that nicotine N-oxide and also the reduction product of cotinine both conferred some protection. The pharmacological basis of the protective effect is not clear but it may involve ganglion-blocking activity; the ganglion-blocking drugs hexamethonium and pempidine also protected mice from the lethal effects of nicotine.

Several amino‐acid esters and amides have been prepared and their toxicological and pharmacological properties have been investigated. Some of the quaternary esters and amides were lethal to mice at doses below 1 mg/kg; this lethality was usually associated with high nicotinic activity. None of the compounds showed high muscarinic activity. The cause of death was asphyxia due to paralysis of the respiratory muscles, but at higher doses there was also failure of the medullary respiratory centre. Administration of sub‐lethal doses of nicotine to mice was shown to protect the animals from subsequent lethal doses of nicotine. The amino‐acid esters did not share this property, nor was there any cross‐protection between nicotine and these esters. The possible nature of the nicotinic receptor is discussed with reference to these compounds and other known nicotinic agents. A tentative suggestion is made that nicotinic activity can result from a two‐point interaction between the drug and the receptor.