Methylergometrine, an active metabolite of methysergide

In conscious dogs methysergide (MS) caused constriction of the saphenous vein at about 3000 times lower doses than methylergometrine (MT) when infused locally, but it elicited only a short-lasting venoconstrictor response when injected systemically intravenously. MS and MT proved to be equally active venoconstrictor agents when administered orally. Analysis of canine plasma by high-performance liquid chromatography showed that after both oral and intravenous administration of MS large amounts of MT appeared in the plasma, whereas only low and transient levels of MS could be detected. It is suggested that one of the first steps in metabolism of MS is demethylation at position 1 of the indole, leading to the formation of MT, which may be a main active principle of the therapeutic effectiveness of MS in the interval treatment of migraine headache.