Henry Hallett Dale (1875–1968), Arthur Stoll (1887–1971), Albert Hofmann (1906–2008)
Ergot has a fascinating history dating back to the Middle Ages, so it is not surprising that during the early years of the twentieth century, Nobel Prize–winning pharmacologist Henry Hallett Dale was attracted to explore its pharmacological properties. Ergot extracts contain a virtual gold mine of unstudied alkaloids produced by the fungus Claviceps purpurea, a contaminant of rye and other grains. In 1917, Swiss biochemist Arthur Stoll became director of pharmacological research at Sandoz (now Novartis) in Basel. His job was to identify active chemicals from natural sources, and the first that he tackled was ergot.
MIGRAINE AND CHILDBIRTH DRUGS. Stoll isolated ergotamine in 1920 and ergonovine in 1935, the latter contemporaneously with other research groups in England and the United States. Ergotamine, ergonovine, and their closely related cousins have had two primary medicinal uses—namely, the treatment of migraine headaches and postpartum bleeding.
The anti-migraine effects of ergotamine are complicated and complex. Migraine headaches are associated with the pulsation (constricting, then widening) of arteries in the brain. Ergotamine may act by opposing this widening. Its ability to stop an attack after an injection is dramatic, but when used too often, in higher doses, or in very sensitive individuals, it can produce signs of ergotism—historically referred to as St. Anthony’s fire—including gangrene affecting the extremities.
Midwives have given extracts of ergot for hundreds of years to cause contractions of the uterus to hasten labor; stillborns often resulted. Ergonovine is now used postpartum and after abortions to decrease bleeding and to promote shrinkage of the uterus.
Both ergotamine and envonovine are chemically lysergic acid derivatives. While studying their chemistry, Albert Hofmann, a colleague of Stoll at Sandoz, developed lysergic acid diethylamide (LSD), discovering its psychedelic effects in 1943.
SEE ALSO Alcohol (c. 10,000 BCE), Ergot (1670), Alkaloids (1806), LSD (1943), Imitrex (1991).
Ergot, the natural source of ergotamine, has been used in childbirth for hundreds of years to stimulate labor contractions. This terra-cotta statuette from South America depicts a woman giving birth.