2501
T3D2460
Ergotamine
Ergotamine is only found in individuals that have used or taken this drug. It is a vasoconstrictor found in ergot of Central Europe. It is an alpha-1 selective adrenergic agonist and is commonly used in the treatment of migraine disorders. Ergotamine acts on migraine by one of two proposed mechanisms: 1) activation of 5-HT<sub>1D</sub> receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache, and 2) activation of 5-HT<sub>1D</sub> receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
113-15-5
8223
C33H35N5O5
581.263820
ErgomarĀ® Sublingual Tablets are round, green tablets each containing 2 mg of ergotamine tartrate.
213.5 decĀ°C
Slight
Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)
The bioavailability of sublingually administered ergotamine has not been determined.
Ergoline alkaloids tend to act as a group, producing complex and variable effects of partial agonism or antagonism at adrenergic, dopaminergic, and serotonergic receptors. Variables relating to these effects are influenced by the agent, dosage, species, tissue, physiological, and endocrinological state, and experimental conditions. In particular, ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. Ergometrine is also known to have a non-receptor specific oxytocic activity. Ergotamine acts on migraine by one of two proposed mechanisms: 1) activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leading to vasoconstriction, which correlates with the relief of migraine headache, and 2) activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system, resulting in the inhibition of pro-inflammatory neuropeptide release. (A2914, A2915, A2916)
Ergotamine is metabolized by the liver by largely undefined pathways, and 90% of the metabolites are excreted in the bile. (A1497)
Half Life: 2 hours
LD50: 62 mg/kg (Intravenous, Rat) (T178)
No indication of carcinogenicity to humans (not listed by IARC).
For use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called "histaminic cephalalgia". Ergotamine is a secondary metabolite (natural product) and principal alkaloid of the ergot fungus, Claviceps purpurea, and related fungi in the family Clavicipitaceae. It is used medicinally for treatment of acute migraine attacks (sometimes in combination with caffeine), and to induce childbirth and prevent post-partum haemorrhage. (L1927)
Vasoconstrictive complications of a serious nature may occur at times. These include ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, EKG changes and muscle pains. Although these effects occur most commonly with long-term therapy at relatively high doses, they have also been reported with short-term or normal doses. Other cardiovascular adverse effects include transient tachycardia or bradycardia and hypertension. Ingestion of ergoline alkaloids is also known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (A1497, L1452, A2913)
Signs of ergotamine overexposure include irritation, nausea, vomiting, headache, diarrhea, thirst, coldness of skin, pruritus, weak pulse, numbness, tingling of extremities, and confusion. Convulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (A1497, L1733, L1920)
Treatment consists of removal of the offending drug. Maintenance of adequate pulmonary ventilation, correction of hypotension, and control of convulsions and blood pressure are important considerations. Treatment of peripheral vasospasm should consist of warmth, but not heat, and protection of the ischemic limbs. Vasodilators may be beneficial but caution must be exercised to avoid aggravating an already existent hypotension. (L1733)
2009-07-03T21:06:25Z
2014-12-24T20:25:32Z
Ergotamine
C07544
64318
D004878
Ergotamine
DB00696
true
[H][C@@]12CCCN1C(=O)[C@]([H])(CC1=CC=CC=C1)N1C(=O)[C@@](C)(O[C@@]21O)N=C(O)[C@@]1([H])CN(C)[C@]2([H])CC3=CNC4=CC=CC(=C34)C2=C1
C33H35N5O5
InChI=1S/C33H35N5O5/c1-32(35-29(39)21-15-23-22-10-6-11-24-28(22)20(17-34-24)16-25(23)36(2)18-21)31(41)38-26(14-19-8-4-3-5-9-19)30(40)37-13-7-12-27(37)33(38,42)43-32/h3-6,8-11,15,17,21,25-27,34,42H,7,12-14,16,18H2,1-2H3,(H,35,39)/t21-,25-,26+,27+,32-,33+/m1/s1
InChIKey=XCGSFFUVFURLIX-VFGNJEKYSA-N
581.6615
581.263819255
Exogenous
Solid
2
HMDB14834
CHEMBL442
7930