The action of an active principle from apocynum / by H.H. Dale and P.P. Laidlaw.

  • Dale, Henry Hallett, 1875-1968.
Date:
1909
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Licence: Attribution 4.0 International (CC BY 4.0)

Credit: The action of an active principle from apocynum / by H.H. Dale and P.P. Laidlaw. Source: Wellcome Collection.

Provider: This material has been provided by The Royal College of Surgeons of England. The original may be consulted at The Royal College of Surgeons of England.

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    Vol. I, No. 2, November, 1909.] THE ACTION OF AN ACTIVE PRINCIPLE FROM APOCYNUM. By H. H. DALE and P. P. LAIDLAW. (From the Physiological Laboratory, Guy's Hospital*, and the Wellcome Physiological Research Laboratories, Herne Hill, S.E.) I. Historical and Introductory. Apocynum has for many years enjoyed a somewhat varying reputation in therapeutics, chiefly as an alterative to digitalis. The earlier clinical observers (Knapp, Grisconl,2) who appear to have tried the drug on the strength of its reputation among the American Indians, describe it as emetic, cathartic, diaphoretic, and diuretic. Later clinical observers, such as Dabney5, laid special emphasis on its diuretic action. Dabney’s paper con- tains a number of references to similar clinical observations. Husemann13 appears to have first pointed out that this drug, like other members of the Apocynacae (Oleander, Strophanthus), contained a heart-poison belonging to the Digitalis group. Bradford is reported by Murray19 to have found that it resembled Strophanthus in its action on the heart, but that its powerful effect on the vagus mechanism, and the absence of a vaso-constrictor effect, prevented it from producing any rise of blood pressure. In 1883 Schmiedeberg22 separated from it two indefinite products which he termed Apocynin and Apocynein. Apocynin was an amorphous non-glucosidal body, almost insoluble in water, readily soluble in alcohol and ether, which caused systolic arrest of the frog’s heart in very small doses. Apocynein was an amorphous glucoside resembling digitalein. In 1888 Sokoloff23 examined the action of Apocynum on mammals. He found that an extract (he used an 8 per cent, watery infusion of the rhizome), when injected intravenously in doses of from 3 to 10 cc., caused, in the first place, a pronounced retardation of the heart’s action, the pulse wave being enlarged, and the blood pressure raised ; later, the initial retardation gave way to a secondary acceleration of the heart, the arterial pressure rising still further. He stated that the initial slowing of the heart was caused by a stimulation of the cardio-inhibitory centre, and of the peripheral inhibitory mechanism. The subsequent acceleration was not due to actual paralysis of the inhibitory apparatus, since injection of another dose of the drug could again produce retardation. Large doses produced a third stage of arrhythmia * The experiments at Guy’s Hospital were performed by P. P. Laidlaw only. Vol. I, No. 2.