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Ergotamine



Ergotamine
Systematic (IUPAC) name
Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(phenylmethyl)-, (5'-alpha)- (9CI)
Identifiers
CAS number 113-15-5
ATC code N02CA02
PubChem 9787
Chemical data
Formula C33H35N5O5 
Mol. mass 581.66 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism hepatic
Half life  ?
Excretion renal
Therapeutic considerations
Pregnancy cat.

?

Legal status

Prescription Only (S4)(AU) POM(UK) -only(US)

Routes Oral

Ergotamine is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor. It is used medicinally for migraine prevention (sometimes in combination with caffeine), and to induce childbirth and prevent post-partum haemorrhage.

Additional recommended knowledge

Contents

Mechanism of action

The mechanism of action of ergotamine is complex. The molecule shares similarity with neurotransmitters such as serotonin, dopamine, and adrenaline and can thus bind to several cell receptors acting both as agonist and antagonist in signal transduction within cellular tissues. The anti-migraine effect is due to constriction of the intercranial extracerebral blood vessels through the 5-HT1B receptor, and by inhibiting trigeminal neurotransmission by 5-HT1D receptors. Ergotamine also has effects on the dopamine and noradrenaline receptors. It is its action on the D2 dopamine and 5-HT1A receptors that can cause some side effects. [1]

Biosynthesis

Ergotamine is a secondary metabolite (natural product) and the principal alkaloid produced by the ergot fungus, Claviceps purpurea, and related fungi in the family Clavicipitaceae. Its biosynthesis in these fungi requires the amino acid, L-tryptophan, and dimethylallyl diphosphate. These precursor compounds are the substrates for the enzyme, dimethylally-tryptophan (DMAT) synthase, catalyzing the first step in ergot alkaloid biosynthesis, i.e., the prenylation of L-tryptophan. Further reactions, involving methyltransferase and oxygenase enzymes, yield the ergoline, lysergic acid. Lysergic acid (LA) is the substrate of lysergyl peptide synthetase, a nonribosomal peptide synthetase, which covalently links LA to the amino acids, L-alanine, L-proline, and L-phenylalanine. Enzyme-catalyzed or spontaneous cyclizations, oxygenations/oxidations, and isomerizations at selected residues precede, and give rise to, formation of ergotamine.[2]

Illegal uses

Ergotamine is also a precursor of LSD, lysergic acid diethylamide.

See also

  • Cafergot, a preventative migraine treatment with ergotamine and caffeine.

References

  1. ^ Tfelt-Hansen P, Saxena PR, Dahlof C, Pascual J, Lainez M, Henry P, Diener H, Schoenen J, Ferrari MD, Goadsby PJ (2000). "Ergotamine in the acute treatment of migraine: a review and European consensus". Brain 123: 9-18. PMID 10611116.
  2. ^ Schardl CL, Panaccione DG, Tudzynski P (2006). "Ergot alkaloids--biology and molecular biology". Alkaloids Chem. Biol. 63: 45-86. PMID 17133714.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Ergotamine". A list of authors is available in Wikipedia.
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