migrane vs ergotamine

Ergotamine
Systematic (IUPAC) name
(6aR,9R)-N-((2R,5S,10aS,10bS)- 5-benzyl-10b-hydroxy-2-methyl- 3,6-dioxooctahydro-2H-oxazolo[3,2-a] pyrrolo[2,1-c]pyrazin-2-yl) -7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg] quinoline-9-carboxamide
Identifiers
CAS number 113-15-5
ATC code N02CA02
PubChem 9787
ChemSpider 7930
Chemical data
Formula C33H35N5O5
Mol. mass 581.66 g/mol
Pharmacokinetic data
Bioavailability ?
Metabolism hepatic
Half life ?
Excretion renal
Therapeutic considerations
Pregnancy cat.
X(US)
Legal status
bb(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 treatment of acute migraine attacks (sometimes in combination with caffeine), and to induce childbirth and prevent post-partum haemorrhage. It was first isolated from the ergot fungus by Arthur Stoll at Sandoz in 1918 and marketed as Gynergen in 1921.

Mechanism of action
The mechanism of action of ergotamine is complex.[2] 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. [3]

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, dimethylallyl-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.[4]
Drug uses
Ergotamine is also a precursor of LSD, lysergic acid diethylamide. It produces vasoconstriction peripherally. It damages the peripheral epithelium and in high doses is conducive to the creation of vascular stasis, thrombosis and gangrene. It can increase uterine contractivity and occasionally is used therapeutically immediately post-partum to decrease uterine bleeding. It continues to be prescribed for migraines. Contraindications include: atherosclerosis, Buerger's syndrome, coronary artery disease, hepatic disease, pregnancy, pruritus, Raynaud's syndrome, and renal disease. [5]
See also
* Cafergot, an abortive migraine treatment with ergotamine and caffeine.
References 1. ^ AJ Giannini, AE Slaby. Drugs of Abuse. Oradell, NJ, Medical Economics Books, 1989.
2. ^ Walkembach J, Brüss M, Urban BW, Barann M (October 2005). "Interactions of metoclopramide and ergotamine with human 5-HT(3A) receptors and human 5-HT reuptake carriers". Br. J. Pharmacol. 146 (4): 543–52. doi:10.1038/sj.bjp.0706351. PMID 16041395. PMC: 1751187. http://dx.doi.org/10.1038/sj.bjp.0706351.
3. ^ 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. doi:10.1093/brain/123.1.9. PMID 10611116.
4. ^ Schardl CL, Panaccione DG, Tudzynski P (2006). "Ergot alkaloids--biology and molecular biology". Alkaloids Chem. Biol. 63: 45–86. doi:10.1016/S1099-4831(06)63002-2. PMID 17133714.
5. ^ AJ Giannini. Biological Foundations of Clinical Psychiatry. Oradell, NJ. Medical Economics Puclishing Co., 1986.

Aku adalah salah seorang pesakit migrain peringkat pertengahan..Jadi tiap2 kali bila aku rasa sakit sampai tak bulih tahan, aku akan ambik pil cafergot nie.Ingat kan tak pe lah sebab pil ni banyak tolong aku walau pon aku bukannya ambik kerap.Cuma bila aku dah tak tahan saja baru aku ambik. Lama jugak ambik ubat nie..dari tahun 2004 lagi..Doktor kata kandungan oksigen dalam otak kurang..sebab tu lah migrain nie jadi..entah betoi ka dak aku terpaksa percaya kata doktor tu..katanya lagi mungkin aku stress dalam kerja...maybe !!
Baru lima enam bulan lepas aku tau yang ubat ni ada kandungan dadah...betoi lah tu sebab dalam kandungan dia ada ergotamin dan caffein..lagi pon semua ubat tu memang ada dadah..bohong lah kalu ubat tak ada dadah..Ishh satu lagi masaalah timboi..urine test aku sangkut pulak dah sampai nak kena pi tesk kat AADK...aku pon heran sebab dalam urine tu ada kandungan methampetamine..Heran jugak !!!..yang pastinya aku tak pernah kenai pon benda kotor tu..atau mungkin kah alat yang depa guna tu tak tepat keputusan nya..atau adakah aku nie kena naiya..apa2 pon bagi aku ni dah kira kes naya nie..Nasib aku sebab lepas buat test kali kedua tak menunjukan aku ambik metaphentamine.bukan pasal apa..sebab minggu tu aku tak kena migrain....nasibbb..