1. Mechanism of action

2. Biosynthesis

3. Drug uses

4. Availability and dosage

5. Side effects

6. Additional Information

7. See also

8. References

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). Medicinal usage of ergot fungus began in the 16th century to induce childbirth, yet dosage uncertainties discouraged the use. It has been used to prevent post-partum hemorrhage (bleeding after childbirth). It was first isolated from the ergot fungus by Arthur Stoll at Sandoz in 1918 and marketed as Gynergen in 1921.^[4]

Mechanism of action

The mechanism of action of ergotamine is complex.^[5] The molecule shares structural similarity with neurotransmitters such as serotonin, dopamine, and epinephrine and can thus bind to several receptors acting as an agonist. The anti-migraine effect is due to constriction of the intracranial extracerebral blood vessels through the 5-HT_1B receptor, and by inhibiting trigeminal neurotransmission by 5-HT_1D receptors. Ergotamine also has effects on the dopamine and norepinephrine receptors.

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.^[6] Its biosynthesis in these fungi requires the amino acid L-tryptophan and dimethylallyl diphosphate. These precursor compounds are the substrates for the enzyme, tryptophan dimethylallyltransferase, 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.^[7]

Drug uses

Ergotamine produces vasoconstriction peripherally as well as damages the peripheral epithelium. In high doses, ergotamine is conducive to vascular stasis, thrombosis, and gangrene. It can increase uterine contractivity and occasionally is used therapeutically immediately post-partum to decrease uterine bleeding. See also ergometrine.

Ergotamine continues to be prescribed for migraines. The common form of prescription is Cafergot which is a combination of caffeine and ergotamine.

Contraindications include: atherosclerosis, Buerger's syndrome, coronary artery disease, hepatic disease, pregnancy, pruritus, Raynaud's syndrome, and renal disease.^[8]

It's also contraindicated if patient is taking Macrolide antibiotics (eg, erythromycin), certain HIV protease inhibitors (eg, ritonavir, nelfinavir, indinavir), certain azole antifungals (eg, ketoconazole, itraconazole, voriconazole) delavirdine, efavirenz or a 5-HT1 agonist (eg, sumatriptan).

Availability and dosage

In the United States, ergotamine is available as a suppository, a sublingual tablet, and a tablet, sometimes in combination with caffeine. The suppository is available under the brand name Migergot, which contains 2 mg of ergotamine with 100 mg caffeine. The sublingual tablet is available under the brand name Ergomar and contains 2 mg of ergotamine. The combination tablet in combination with caffeine called Cafergot contains 1 mg of ergotamine and 100 mg of caffeine.^[10]

This preparation may be used immediately following the aura/onset of pain to abort the migraine. For the best results, dosage should start at the first sign of an attack.^[11]

Side effects

Side effects of ergotamine include nausea and vomiting. At higher doses, it can cause raised arterial blood pressure, vasoconstriction (including coronary vasospasm) and bradycardia or tachycardia. Severe vasoconstriction may cause symptoms of intermittent claudication.^[12]

Additional Information

Ergotamine is a controlled substance in the United States as it is a commonly used precursor for the production of LSD.^[13]

See also

• Dihydroergotamine, a semi-synthetic form used as an abortive migraine treatment
• Ergotism
• Ergometrine

References

• 1035 BC
• 1036
• 1036 BC
• 1036 Ganymed
• 1037
• 1037 BC
• 1038
• 1038 BC
• 1039
• 1039 BC
• 1039/Smoothed Out Slappy Hour
• 1,039/Smoothed Out Slappy Hour
• 1039 Smoothed Out Slappy Hours
• 1,039/Smoothed Out Slappy Hours
• 1039/Smoothed Out Slappy Hours
• 103 AD
• 103 BC
• 103 BCE
• 103 Colmore Row
• 103-form Yang family tai chi chuan
• 103 Hera
• 103 (number)
• 103rd Congress
• 103rd Infantry Division (United States)
• 103rd (Lancastrian Artillery Volunteers) Regiment Royal Artillery