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.

[2][22] 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".

[23] 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.

In 1943, Arthur Stoll and Albert Hofmann reported the first total synthesis of an ergot alkaloid, ergometrine.

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.

Drugs such as bromocriptine act as a dopamine receptor agonist, stimulating the nerves that control movement.

[28] Newer synthetic ergoline derivatives that have been synthesized for the treatment of Parkinson's disease include pergolide and lisuride, which both act as dopamine agonists as well.

Ergometrine and ergotamine are included as schedule I precursors in the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.

[30] Ergoline alkaloids often interfere with multiple receptor sites, leading to negative side effects and adding to the challenge of drug development.

Thus, it was concluded that ergotoxin, and related ergolines, act via the hypothalamus and pituitary gland to inhibit the secretion of prolactin.

[30] The primary challenges of developing serotonergic/antiserotonergic ergolines is attributed to serotonin, or 5-HT, acting on various distinct receptor sites.

Ergopeptines are considered to be the most toxic and are capable of inducing gangrene: “The low molecular ergolines are lacking the complex peptide moiety, which is apparently responsible for the persistence of the ergopeptines at the receptor molecules.”[36] A variety of modifications to the basic ergoline are seen in nature, for example agroclavine, elymoclavine, lysergol.

Some examples are: Morning glory: Argyreia nervosa (Hawaiian Baby Woodrose), Ipomoea spp.