Ergotamine
Cafergot (with caffeine), Ergomar, others | |
| Other names | 2'-Methyl-5'α-benzyl-12'-hydroxy-3',6',18-trioxoergotaman; 9,10α-Dihydro-12'-hydroxy-2'-methyl-5'α-(phenylmethyl)ergotaman-3',6',18-trione |
|---|---|
| AHFS/Drugs.com | Monograph |
| Routes of administration | Oral |
| ATC code | |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | Intravenous: 100%,[2] Intramuscular: 47%,[3] Oral: <1%[4] (Enhanced by co-administration of caffeine[2]) |
| Metabolism | Hepatic[3] |
| Elimination half-life | 2 hours[3] |
| Excretion | 90% biliary[3] |
| Identifiers | |
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Ergotamine, sold under the brand names Cafergot (with
vasoconstrictor
.
It is used for acute
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.[6]
Biosynthesis
Ergotamine is a
oxidations, and isomerizations at selected residues precede, and give rise to, formation of ergotamine.[8]
Medical uses
Ergotamine continues to be prescribed for migraines and cluster headaches.[9]
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]
Contraindications
Contraindications include:
Raynaud's syndrome, and renal disease.[12]
It's also contraindicated if patient is taking 5-HT1 receptor agonist (e.g., sumatriptan
).
[13]
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.[14][9]
Pharmacology
Pharmacodynamics
Ergotamine interacts with
hallucinogenic similarly to lisuride.[18][19] This is thought to be due to functional selectivity at the 5-HT2A receptor.[18][19]
| 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). CB1, GABA, glutamate, or nicotinic acetylcholine receptors, nor the monoamine transporters (all >10,000 nM).[16]
| |||
Pharmacokinetics
The
first-pass metabolism.[15]
Legal status
Ergotamine is included as a List I precursor in the United States, as it is a commonly used precursor for the production of LSD.[24]
See also
References
- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-15.
- ^ S2CID 37538721.
- ^ a b c d Tfelt-Hansen P, Johnson ES (1993). "Ergotamine". In Olesen J, Tfelt-Hansen P, Welch KM (eds.). The Headaches. New York: Raven Press. pp. 313–22.
- PMID 6419759.
- ISBN 978-3-88763-075-1.
- ^ A. J. Giannini, A. E. Slaby. Drugs of Abuse. Oradell, New Jersey: Medical Economics Books, 1989.
- ^ "Pharmacognosy of Ergot (Argot or St. Anthony's Fire)". pharmaxchange.info. 30 December 2011. Archived from the original on 17 July 2012.
- PMID 17133714.
- ^ S2CID 22768662.
- ^ "Approved Drug Products". FDA Orange Book (40th ed.). U.S. Food and Drug Administration. 2020.
- ^ "CAFERGOT- ergotamine tartrate and caffeine tablet, film coated". DailyMed. U.S. National Library of Medicine. Archived from the original on 2014-01-16.
- ^ Giannini AJ (1986). Biological Foundations of Clinical Psychiatry. Oradell, NJ: Medical Economics Publishing Co.
- ^ "Ergotamine: Indications, Side Effects, Warnings". Drugs.com. Archived from the original on 25 March 2017. Retrieved 25 March 2017.
- ^ "Medihaler Ergotamine". drugs.com. Archived from the original on 2016-04-01. Retrieved 2016-05-20.
- ^ S2CID 22721405.
- ^ a b c d PDSP Database – UNC
- PMID 24361689.
- ^ PMID 24637012.
- ^ ISBN 978-0-12-800212-4.
- S2CID 21356727.
- PMID 11104741.
- PMID 31418454.
- PMID 20945968.
- ^ "Lists of: Scheduling Actions, Controlled Substances, Regulated Chemicals" (PDF). Drug Enforcement Administration, Diversion Control Division, Drug & Chemical Evaluation Section. U.S. Department of Justice. February 2020.