Ergotamine is a main alkaloid of the ergot fungus. It is a highly effective substance (see LD50), which among other things, is partly responsible for ergot poisoning (Anthony’s fire). Therapeutic ergotamine can be used for the acute treatment of migraine and for short-term prophylaxis of cluster headaches. The substance was isolated in 1918 by Arthur Stoll.
Ergotamine is chemically a condensation product of lysergic acid and a tricyclic tripeptide of alanine, phenylalanine and proline dar. The extraction of ergotamine from the ergot fungus takes place, which is cultivated for that purpose, for example, on rye.
Ergotamine shows to α1 high (nanomolar and subnanomolar) affinity-and α2-adrenoceptors, dopamine receptors and serotonin (5-HT) receptors. At these receptors, it acts as an agonist, partial agonist or antagonist. The LD50 value is 3.0 mg / kg (rabbit, iv).
The plasma half-life is 20-34 hours. Its migraine efficacy is justified by the partial agonist effect of ergotamine on 5-HT1B/1D to blood vessels in the CNS. Ergotamine, not only from a pharmacodynamic point of view (lack of selectivity), but also from pharmacokinetic point of view is problematic (small, noisy absorption, poor tissue penetration and relatively long half-life), therefore making it third choice for the acute treatment of migraine.
Ergotamine is one of the secondary metabolites and is the main alkaloid of the ergot fungus (Claviceps purpurea). The ergotamine biosynthesis of this closely related fungi begins with the condensation of the amino acid, L-tryptophan by prenylation with dimethylallyl diphosphate, which is catalyzed by the enzyme Dimethylally-tryptophan (DMAT) synthase.
This first biosynthetic step is common to all ergot alkaloids, and after a number of other enzymatic steps oxygenases and methyltransferases, the ergoline lysergic acid is formed. Lysergic acid is in the subsequent steps of the enzyme Lysergyl peptide synthetase as a substrate and successively bound to L-alanine, L-proline and L-phenylalanine. In several steps the enzymatic expires or spontaneous ring closes, and oxygenation and epimerization ergotamine is finally revealed as the final product.
Terms and conditions
Since ergotamine is used as a raw material for the synthesis of the banned hallucinogen LSD, supply is limited in practice worldwide by the respective raw surveillance laws.
Ergo Headaches (D)
Cafergot (D, CH)