A PRELIMINARY note on the phenomena dealt with more completely in this paper was entitled, " The Physiological Action of Chrysotoxin'." Since the date of that publication further experiment has shown that the action is due to a principle, or combination of principles, which, by the aid of the physiological test, can be recognised in the various substances for which the title of "active principle" has been claimed, and indeed in all preparations of ergot possessing therapeutic activity. The active resin extracted from chrysotoxin, and called by Jacobj2 " sphacelotoxin," gives the effect in doses of a few milligrammes. So also do preparations corresponding in mode of extraction and solubility to the " cornutine" of Kobert, and differing from that substance only in their failure to elicit the spasms in frogs, described by Kobert3 as characteristic-a failure by no means unique in the experience of those who have worked with "cornutine" since Kobert. A resinous substance separated from commercial ergotinine also gives the reaction very typically and in small dosages; while, in larger quantities, many specimens of the ordinary pharmacopceial extracts produce the same effects, complicated only by the' presence of depressant impurities.These facts make it impossible to speak of the action any longer as that of chrysotoxin. On the other hand, the wide acceptance of Kobert's4 view as to the difference between spbacelotoxin (in -sphacelinic acid) and cornutine would render the attribution of the effects to either of those substances misleading. The introduction of new names on the strength of physiological results, and in default of chemical isolation of principles, would inevitably add to the existing confusion, 1

IMINAZOLYLETHYLAMINE is the amine which is produced when carbon dioxide is split off from histidine. It was first prepared synthetically by Windaus and Vogt'. Recently Ackermann2 obtained a large yield of the base by submitting histidine to the action of putrefactive organisms. It has been shown that several of the amines thus related to amino-acids possess marked physiological activity. The activity of j8-iminazolylethylamine was discovered in the course of the investigation of ergot and its extracts by G. Barger and one of us3, who attributed this structure to a base which they obtained, and which in minute doses produced tonic contraction of the uterus. The synthetic substance, and the base produced by splitting off carbon dioxide from histidine by bacterial action or by chemical means, were found to have an identical action. Meanwhile Kutscher4 had simultaneously and independently described the isolation from ergot of a base having this action and presumably identical with that obtained by Barger and Dale. By its chemical properties this first ergot base of Kutscher was not distinguishable from 8-iminazolylethylamine; but certain apparent differences in the physiological action of the two bases, observed by Ackermann and Kutscber-5, led them to the conclusion that the ergot base, though closely related to 8-iminazolylethylamine, is not identical with it. The alleged difference in action, on the existence and cause of which our experiments throw light, was as follows: the 1 Ber. d. deutsch. chem. Gesell. xi,. p. 3691. 1907.

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IN a note published some time ago [Dale and Feldberg, 1934] [1932] and Plattner [1932, 1933] found that the substance present in such extracts was rapidly inactivated by fresh blood, like acetylcholine, and that the quantity present had a general correspondence to the wide differences in sensitiveness of different muscles to the stimulating action of acetylcholine. Faradic stimulation of the nerve increased the yield; but P1 attn e r associated the apparent presence of the acetylcholine in the muscle, and its increase on mixed nerve stimulation, with a "parasympathetic" innervation of the blood vessels. In the tongue, excised from a cat treated with eserine, and divided longitudinally into halves, he found that stimulation of the chorda-lingual nerve caused increase of acetylcholine in the extract from one half, while stimulation of the hypoglossal nerve did not significantly increase the yield of the other.Hess [1923], Brinkman and Ruiter [1924, 1925]

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