Ergotamine – University of Copenhagen

NaToxAq > Toxin of the week > Ergotamine

10 September 2018

Ergotamine

Natural toxin

Ergotamine is a naturally occurring ergot alkaloid. It causes constriction of blood vessels.

Ergot alkaloids are a group of natural biologically active compounds belonging to indole derivatives that occur in both fungi and higher plants. They are mainly produced by the fungal pathogens – Claviceps purpurea –in the ears of various Poaceae like rye, triticale, wheat, barley and sorghum, although rye is the most affected one (Figure 1).  They also occur in the seeds of morning glory plant, Ipomoea tricolor from the Convolvulaceae. The long term exposure to ergot alkaloid causes ergotism in humans and other mammals.

Figure 1: An ergot in rye (a) and barely, and (c) convulsive symptoms of ergotism.

Ergotamine (an ergot alkaloid) is a naturally occurring secondary metabolite containing tetracyclic ring system of ergoline. Clinically, it has analgesic property and, in obstetrics, used as a haemostatic. From medicinal perspectives, it is a drug of choice for the treatment of acute migraine attacks (sometimes in combination with caffeine).

Figure 2: The chemical structure of ergotamine. Click image for interactive 3D model

Ergotamine is highly toxic, alpha adrenoreceptor antagonist and potent vasoconstrictor. In the intracranial blood vessels, it selectively binds and activates serotonin (5-HT) 1D receptors causing reduced blood flow in cerebral arteries, which results in vascular headaches. It is also responsible for the gangrenous infections.  Due to extensive first-pass elimination in the liver, the bioavailability of ergotamine is only a few percent. However, the pharmacodynamic response lasts longer.

The common symptom include sudden numbness or weakness, hallucinations, delirium, convulsions, problems with speech, muscle pain in arms or legs and fast or slow heart rate.

CAS No: 113-15-5

SMILES:  CC1(C(=O)N2C(C(=O)N3CCCC3C2(O1)O)CC4=CC=CC=C4)NC(=O)C5CN(C6CC7=CNC8=CC=CC(=C78)C6=C5)C

References:

  • P. Tfelt-Hansen, P.R. Saxena, C. Dahlöf, J. Pascual, M. Láinez, P. Henry, H. Diener, J. Schoenen, M.D. Ferrari, P.J. Goadsby (2000). Ergotamine in the acute treatment of migraine: a review and European consensus. Brain 123:9-18.
  • C. Müller, H.S. Klaffke, W. Krauthause, R. Wittkowski (2006). Determination of ergot alkaloids in rye and rye flour. Mycotoxin Research 22 (4): 197-200.
  • C. Colin (2015).  Review – Analysis of ergot alkaloids. Toxins 7: 2024-2050.
  • U. Steiner, E. Leistner (2018).  Ergot alkaloids and their hallucinogenic potential in morning glories. Planta Med 84: 751–758.

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