Ergotamine

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| _other_data=(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

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Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline.<ref name="IndexNominum2000">Template:Cite book</ref> It is structurally similar to several neurotransmitters, and it acts as a vasoconstrictor. It is used for acute migraines, sometimes with caffeine as the combination ergotamine/caffeine.<ref name="Cafergot FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Migergot FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The drug is a non-selective modulator or agonist of serotonin receptors and other receptors.<ref name="pmid23815106" /><ref name="PDSPKiDatabase" /><ref name="KehlerLindskov2025" /> It is peripherally selective and crosses into the brain in minimal amounts.<ref name="KehlerLindskov2025">Template:Cite journal</ref>

Medicinal use of ergot fungus began in the 16th century, for the induction of childbirth; but dosage uncertainty discouraged its 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 was marketed as Gynergen in 1921.<ref>A. J. Giannini, A. E. Slaby. Drugs of Abuse. Oradell, New Jersey: Medical Economics Books, 1989.</ref>

Medical uses

Ergotamine is indicated as therapy to abort or prevent vascular headache.<ref name="Ergomar FDA label" /><ref name="myths">Template:Cite journal</ref>

Available forms

Ergotamine is available as a suppository and as a tablet, sometimes in combination with caffeine.<ref name="Ergomar FDA label" /><ref name="Ergomar sublingual FDA label" /><ref name="Cafergot FDA label" /><ref name="Migergot FDA label" />

Contraindications

Contraindications include: atherosclerosis, Buerger's syndrome, coronary artery disease, hepatic disease, pregnancy, pruritus, Raynaud's syndrome, and renal disease.<ref>Template:Cite book</ref> It's also contraindicated if patient is taking macrolide antibiotics (e.g., erythromycin), certain HIV protease inhibitors (e.g., ritonavir, nelfinavir, indinavir), certain azole antifungals (e.g., ketoconazole, itraconazole, voriconazole) delavirdine, efavirenz, or a 5-HT₁ receptor agonist (e.g., sumatriptan).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="myths"/>

Pharmacology

Pharmacodynamics

Ergotamine interacts with serotonin, adrenergic, and dopamine receptors.<ref name="pmid23815106">Template:Cite journal</ref><ref name="PDSPKiDatabase" /><ref name="KehlerLindskov2025" /> It is an agonist of serotonin receptors including the serotonin 5-HT₁ and 5-HT₂ subtypes.<ref name="pmid23815106" /><ref name="KehlerLindskov2025" /> Ergotamine is an agonist of the serotonin 5-HT_2B receptor and has been associated with cardiac valvulopathy.<ref name="pmid24361689">Template:Cite journal</ref> Despite acting as a potent serotonin 5-HT_2A receptor agonist, ergotamine is said to be non-hallucinogenic similarly to lisuride.<ref name="KehlerLindskov2025" /><ref name="pmid24637012">Template:Cite journal</ref><ref name="HanksGonzález-Maeso2016">Template:Cite book</ref> This has been posited to be due to functional selectivity at the serotonin 5-HT_2A receptor.<ref name="pmid24637012" /><ref name="HanksGonzález-Maeso2016" /> However, ergotamine is also peripherally selective, which may instead account for its lack of psychedelic effects.<ref name="KehlerLindskov2025" /><ref name="Canal2018" /><ref name="VerhoeffVisserFerrari1993" />

Template:Nowrap

Site	Affinity (Ki/IC50 [nM])	Efficacy (Emax [%])	Action
5-HT1A	0.17–0.3	?	Full agonist
5-HT1B	0.3–4.7	?	Agonist
5-HT1D	0.3–6.0	?	Agonist
5-HT1E	19–840	?	?
5-HT1F	170–171	?	?
5-HT2A	0.64–0.97	?	Full agonist
5-HT2B	1.3–45	?	Partial agonist
5-HT2C	1.9–9.8	?	Partial agonist
5-HT3	>10,000	–	–
5-HT4	65	?	?
5-HT5A	14	?	Agonist
5-HT5B	3.2–16	?	?
5-HT6	12	?	?
5-HT7	1,291	?	Agonist
α1A	15–>10,000	–	–
α1B	12–>10,000	–	–
α1D	?	?	?
α2A	106	?	?
α2B	88	?	?
α2C	>10,000	–	–
β1	>10,000	–	–
β2	>10,000	–	–
D1	>10,000	–	–
D2	4.0–>10,000	–	Agonist
D3	3.2–>10,000	–	–
D4	12–>10,000	–	–
D5	170	?	?
H1	>10,000	–	–
H2	>10,000	–	–
M1	862	?	?
M2	911	?	?
M3	>10,000	–	–
M4	>10,000	–	–
M5	>10,000	–	–
Notes: All receptors are human except 5-HT5A (mouse/rat) and 5-HT5B (mouse/rat—no human counterpart).<ref name="PDSPKiDatabase" /> No affinity for histamine H1 or H2, cannabinoid CB1, GABA, glutamate, or nicotinic acetylcholine receptors, nor the monoamine transporters (all >10,000 nM).<ref name="PDSPKiDatabase" />

Pharmacokinetics

The bioavailability of ergotamine is around 2% orally, 6% rectally, and 100% by intramuscular or intravenous injection.<ref name="pmid23815106" /> The low oral and rectal bioavailability is due to low gastrointestinal absorption and high first-pass metabolism.<ref name="pmid23815106" />

However, ergotamine does not readily cross the blood–brain barrier and hence is peripherally selective.<ref name="KehlerLindskov2025" /><ref name="Canal2018">Template:Cite journal</ref><ref name="VerhoeffVisserFerrari1993">Template:Cite journal</ref> This is due to it being an avid substrate for P-glycoprotein and breast cancer resistance protein (BCRP).<ref name="KehlerLindskov2025" /> Only minimal amounts of the drug (~1%) cross into the brain.<ref name="KehlerLindskov2025" />

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Unreliable medical source Its biosynthesis in these fungi requires the amino acid L-tryptophan and dimethylallyl pyrophosphate. 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.<ref name="Schardl">Template:Cite book</ref>

Society and culture

Legal status

Ergotamine is a List I regulated chemical in the United States.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

External links

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