Der Rote Keulenkopf

Abstract

In 1935 the English chemist Howard Ward Dudley and the Scottish gynecologist Chassar Moir isolated the highly potent, uterotonic ergometrine from the sclerotia of ergot. Research teams in England and the USA recognized that all ergot alkaloids, known at that time, contained an identical building block, which was named “lysergic acid”. This new insight motivated the Swiss natural products chemist Albert Hofmann to start the medicinal-chemical and pharmacological lysergic acid research at Sandoz. For the first time, he elaborated a synthetic route to ergometrine starting from lysergic acid, in the course of which he discovered methylergometrine. In 1946 this new drug substance was approved as a therapeutic for labor induction and for the control of postpartum bleeding. During his research on the discovery of new circulation-stimulating agents, Hofmann synthetized the diethylamide of the lysergic acid (LSD) and recognized its psychotogenic activity by chance. The discovery of LSD reanimated the debate within psychiatry at that time, regarding whether endogenous “toxins” might be the reason for schizophrenia. The discovery of 5-hydroxytryptamine in the brain of vertebrate animals, and its ability to inhibit the psychotropic activity of LSD, paved the way to describing the mind and its diseases on a chemical basis. This relationship would allow the development of low molecular weight compounds for the treatment of psychiatric disorders as an innovative therapeutic option. When, at the Weizmann Institute in Israel, the inhibition of prolactine secretion by ergotoxin was shown, Sandoz, the Italian pharmaceutical company Farmitalia, and a Czech research group started drug development programs from which the new class of specific dopamine D2 receptor agonists evolved. In 1975, Sandoz introduced its 2-bromo-α-ergocryptine for the treatment of hyperprolactinemia and thereby caused female infertility, further accompanying symptoms caused by a prolactinoma, of the acromegaly or of the Parkinson's Disease. In 1975, Sandoz introduced its 2-bromo-α-ergocryptine for the treatment of Parkinson's Disease and of female infertility, acromegaly, and further symptoms caused by prolactin- and growth-hormone-secreting pituitary adenomas.