ON THE TRUE METHYL CHOLINES

In 1914 Dale published his now famous paper on â€oe¿ The action of certain esters and ethers of choline and their relation to mus canine.― In it he described in detail the muscarine action of a certain number of choline derivatives and especially of acetyl choline showing the parallelism between this type of action and the result of stimulation of the parasympathetic nervous system. He also called attention to the great instability of acetyl choline in alkaline solution and to the probability of the existence in blood of an esterase which â€oe¿ contributes to the removal of the active ester from the circulation.― In the same paper the nicotine action of the choline derivatives was described and it was explained that the rise of blood pressure which they cause after atropine in favorable conditions is due to a stimulation of the sympathetic ganglion cells and also in part to a liberation of adrenaline from the suprarenals. Dale also insisted upon the dissimilarity between the choline derivatives, which all possess the so-called nicotine action, and natural muscanine which is devoid of such properties and said (p. 185): The absence of the action [nicotine]in the case of muscarine may raise some doubt as to whether this substance be, indeed, a choline derivative and a quaternary ammonium base. There seems little doubt, however, as to its close chemical relationship with choline