History of Triptans
Did you know that the creation of triptans such as Zomig and Maxalt was inspired by a toxic fungus? To know the fascinating history of ergots, read this article!
Imitrex, Zomig, Maxalt, Relpax, Axert, Frova, Amerge… these pills are sort of the heirs of ancient molecules such as Cafergot (ergotamine + caffeine). But where do these drugs come from? Once again, Mother Nature inspired us. It all begins in the Middle Ages. Rye bread is part of the diet of monks and peasants. Unfortunately, in rainy conditions, rye is sometimes attacked by a fungus: Claviceps purpurea. This fungus vaguely resembles a chicken ergot attached to rye, hence the name “ergot”. Harvested with the cereal, it is then grinded and mixed with flour. It contains a substance (later called ergotamine) which stimulates arteries and the brain’s receptors for serotonin. Consequences can be catastrophic: hallucinations and gangrene. Indeed, the small arteries of extremities contract, and feet and hands die from lack of blood. This is extremely painful: it was called St. Anthony’s fire or holy fire. To heal, sick people would go on a pilgrimage to pray for St. Anthony. This pilgrimage was thought to be miraculous, but in fact, blood circulation got better and gangrene healed because people stopped eating the spoiled bread. The effects of Claviceps purpurea on arteries are eventually discovered and, in the 19th century, a paste made of crushed rye ergot will be used to treat uterine hemorrhages by constriction of the uterus’ arteries. Ancient observations on migraine seem to show a link between the attack and the dilatation of arteries. Patients feel their temples throbbing, their faces turn red, etc. One thing leading to another, Claviceps purpurea ended up being used for migraines. And the effects were positive. Ergotamine, a medical treatment based on the fungus Claviceps purperea was created. As science progresses, receptors for serotonin, on which ergotamine acts, are discovered. However, the problem of gangrene persists. Patients taking large amounts of ergotamine suffer from peripheral gangrene (then called ergotism). With pharmaceutical progress, a molecule is developed, which acts on serotonin, but with less effect on arteries. Sumatriptan, developed by Glaxo, is marketed in 1980. It was like a miracle. Thousands of patients realize they can stop their attacks without having to stay in bed for days. This advance in science also confirms that migraine is not a nervous attack simulated by the patient, but a real neurological illness created by chemical phenomena in the brain. Another product derived from rye ergot is lysergic acid diethylamide (LSD), a powerful hallucinogen. Nowadays, many types of triptans are available, but they are still contraindicated in patients suffering from vascular diseases (cardiac arrest, angina, stroke, peripheral vascular insufficiency). However, the risk is deemed minimal, since triptans act essentially on brain arteries.