Ergoline

Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.

Others, such as lysergic acid diethylamide, better known as LSD, a semi-synthetic derivative, and ergine, a natural derivative found in Argyreia nervosa, Ipomoea tricolor and related species, are known psychedelic substances.

Ergoline alkaloids are found in fungi such as Claviceps purpurea, Claviceps paspali, and the related Periglandula, which have a permanent, symbiotic bond with numerous flowering vines, most notably, Turbina corymbosa and Ipomoea tricolor (“morning glory”). Ergolines are concentrated in the seeds, which have been used for ages by indigenous central/south Americans (i.e. T. corymbosa seeds are known as ololiuhqui) The principal alkaloids in the seeds appear to be ergine and isoergine, but they're just decomposition products of lysergic acid hydroxyethylamide, isolysergic hydroxyethylamide, lysergic acid hydroxymethylethylamide (syn. ergonovine), and isolysergic acid hydroxymethylethylamide (syn. ergonovinine). All of the other ergolines have been quantified in very small amts. except for penniclavine, which was found to be the predominant ergoline in a 2016 assay of I. tricolor seeds. Ergolines have been identified in 42 Morning Glory species. The only ergolines of these seeds that have been trialed as isolates are ergine, ergonovine, and lysergol, with lysergol showing the weakest effect (refs: Ergine / Psychedelic Effects, Ergometrine / Psychedelic Effects).

Ergoline alkaloids were first isolated from ergot, a fungus that infects rye and causes ergotism or St. Anthony's fire. Reports of the toxic effects due to ergoline alkaloids date back to the 12th century. Ergot also has a long history of medicinal use, which led to attempts to characterize its activity chemically. First reports of its use date back to 1582, where preparations of ergot were used in small doses by midwives to induce strong uterine contractions. The first use of ergoline alkaloids in modern medicine was described in 1808 by John Stearns, an American physician, who had reported on the uterine contractile actions of a preparation of ergot as a remedy for "quickening birth".

Attempts to characterize the activity of ergoline alkaloids began in 1907, with the isolation of ergotoxine by G. Barger and F. H. Carrin. However, the industrial production of ergot alkaloids didn't begin until 1918, when Arthur Stoll patented the isolation of ergotamine tartrate, which was marketed by Sandoz in 1921. Following the determination of the basic chemical structure of the ergot alkaloids in 1930, an era of intensive exploration of synthetic derivatives began and industrial production of ergoline alkaloids exploded, with Sandoz continuing to be the leading company in their production worldwide, up until 1950 when other competitors arose. The company, now renamed Novartis, still retains its leadership in the product of ergot alkaloids. In 1943, Arthur Stoll and Albert Hofmann reported the first total synthesis of an ergot alkaloid, ergometrine. Though the synthesis found no industrial application, this was a huge leap forward in the industry.

There are a variety of clinically useful ergoline derivatives for the purpose of vasoconstriction, the treatment of migraines, and treatment of Parkinson's disease. Ergoline alkaloids found their place in pharmacology long before modern medicine as preparations of ergot were often used by midwives in the 12th century to stimulate childbirth. Following Arthur Stoll's isolation of ergometrine, the therapeutic use of ergoline derivatives became well explored.

The induction of uterine contractions via the preparation of ergot was attributed to ergonovine, an ergoline derivative found in ergot, which is a powerful oxytocic. From this, methergine, a synthetic derivative, was elucidated. While used to facilitate child birth, ergoline derivatives can pass into breast milk and should not be used during breastfeeding. They are uterine contractors that can increase the risk of miscarriage during pregnancy.

Another example of medically relevant ergoline alkaloids is ergotamine, an alkaloid also found in ergot. It acts as a vasoconstrictor and has been reported to control migraines. From ergotamine, the anti-migraine drugs dihydroergotamine and methysergide were developed by Albert Hofmann.