The pharmacology of ergometrine

Abstract

The action of ergot on the human uterus has been a matter of popular tradition for more than three centuries, and for more than a century it has found a recognized application in obstetrical practice. Until recent years, the preparation most commonly employed was an extract made by macerating the drug with water; and this was usually given by the mouth. This widely used watery extract, however, usually contained no significant amount of any of the six or seven alkaloids specific to ergot, which had been isolated from it at wide intervals over a period of about 60 years (ergotinine, ergotoxine, ergotamine, ergotaminine, ψ-ergotinine, sensibamine, and ergoclavine). The same was true of a number of the proprietary preparations which had been widely used in practice. Further, while several of those alkaloids (ergotoxine, ergotamine, sensibamine, ergoclavine) have a powerful, highly characteristic, and identical pharmacological activity when given by parenteral injection, including a stimulant action on the uterus, their actions are relatively weak and irregular when they are given by the mouth. The proteinogenous amines tyramine and histamine, which had been found to occur in extracts of ergot, whether as products of the metabolism of the fungus itself or of putrefactive changes occurring during the extraction, also have different and well-known pharmacological actions when they are injected into the blood-stream, including stimulant actions of different types on the uterus; but they are again almost without action when given by the mouth in doses having relevance to the activity of ergot extracts. The anomalous position had therefore arisen that the active substances known to occur in ergot were either not present in extracts of the drug which had been used widely and with satisfaction for many years, or, if present, were without significant action when administered by the method commonly employed. This anomaly was completely removed when Moir (1932) showed that the old-fashioned watery extract of ergot, containing none of the alkaloids hitherto known, when administered by the mouth to women in the puerperium, promptly evoked a vigorous rhythmic activity of the previously quiescent uterus, as shown by a simple mechanical record; and when Dudley, whose chemical work was controlled at each stage by Moir’s clinical records, isolated a new alkaloid, ergometrine (Dudley and Moir, 1935), much simpler in structure than, though evidently related to, the previously known ergot alkaloids, soluble in water to some extent as a free base, and giving salts which are readily soluble in water, and easily absorbed from the alimentary canal.