Methylergometrine

Methylergometrine
Clinical data
Trade names	Methergine
Other names	Methylergobasine; Methylergobrevin; Methylergonovine
AHFS/Drugs.com	International Drug Names
MedlinePlus	a601077
Pregnancy; category	Contraindicated;
Routes of; administration	Oral
ATC code	G02AB01 (WHO) ;
Legal status
Legal status	In general: ℞ (Prescription only);
Pharmacokinetic data
Metabolism	Liver
Elimination half-life	30–120 min
Excretion	Mostly bile
Identifiers
	IUPAC name N-[(2S)-1-Hydroxybutan-2-yl]-6-methyl-9,10-didehydroergoline-8β-carboxamide;
CAS Number	113-42-8 ;
PubChem CID	8226;
IUPHAR/BPS	150;
ChemSpider	7933 ;
UNII	W53L6FE61V;
ChEMBL	ChEMBL1201356 ;
CompTox Dashboard (EPA)	DTXSID1023283 ;
ECHA InfoCard	100.003.661
Chemical and physical data
Formula	C20H25N3O2
Molar mass	339.439 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	172 °C (342 °F)
Solubility in water	insoluble mg/mL (20 °C)
	SMILES CC[C@@H](CO)NC(=O)[C@@H]2/C=C1/c3cccc4N\C=C(\C[C@H]1N(C)C2)c34;
	InChI InChI=1S/C20H25N3O2/c1-3-14(11-24)22-20(25)13-7-16-15-5-4-6-17-19(15)12(9-21-17)8-18(16)23(2)10-13/h4-7,9,13-14,18,21,24H,3,8,10-11H2,1-2H3,(H,22,25)/t13-,14+,18-/m1/s1 ; Key:UNBRKDKAWYKMIV-QWQRMKEZSA-N ;
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Methylergometrine (also called methylergonovine, methylergobasin, and d-lysergic acid 1-butanol amide) is a synthetic analogue of ergometrine, a psychedelic alkaloid found in ergot, and many species of morning glory. It is a member of the ergoline family and chemically similar to LSD, ergine, ergometrine, and lysergic acid. Due to its oxytocic properties, it has a medical use in obstetrics. According to Jonathan Ott, methylergonovine has LSD-like actions above 2 milligrams, due to its agonistic action at the 5HT_2A-mGlu2 receptor protomers. Clinical efficacy occurs around 200 µg, ten times lower than the hallucinogenic threshold.

Methylergometrine maleate is marketed under the trade name Methergine.

Uses

Obstetric use

Methylergometrine is a smooth muscle constrictor that mostly acts on the uterus. It is most commonly used to prevent or control excessive bleeding following childbirth and spontaneous or elective abortion, and also to aid in expulsion of retained products of conception after a missed abortion (miscarriage in which all or part of the fetus remains in the uterus) and to help deliver the placenta after childbirth. It is available as tablets or injection (IM or IV) or in liquid form to be taken orally.[1][2][3]

Migraine

Methylergometrine is sometimes used for both prevention[4] and acute treatment[5] of migraine. It is an active metabolite of methysergide.

Contraindications

Methylergometrine is contraindicated in patients with hypertension and pre-eclampsia.[1] It is also contraindicated in HIV positive patients taking protease inhibitors, delavirdine and efavirenz (which is also an agonist at the 5HT_2A-mGlu2 receptor protomer and increases the chances of a patient experiencing hallucinations during methylergometrine therapy).[6]

Side effects

Adverse effects include:[1]

Cholinergic effects such as nausea, vomiting, and diarrhea
Dizziness
Pulmonary hypertension
Coronary artery vasoconstriction
Severe systemic hypertension (especially in patients with pre-eclampsia)
Convulsions

In excessive doses, methylergometrine can also lead to cramping, respiratory depression and coma.[1]

Interactions

Methylergometrine likely interacts with drugs that inhibit the liver enzyme CYP3A4, such as azole antifungals, macrolide antibiotics and many HIV drugs. It can also increase constriction of blood vessels caused by sympathomimetic drugs and other ergot alkaloids.[1]

Mechanism of action

Methylergometrine is a partial agonist/antagonist on serotonergic, dopaminergic and alpha-adrenergic receptors. Its specific binding and activation pattern on these receptors leads to a highly, if not completely, specific contraction of smooth uterus muscle via 5-HT_2A serotonin receptors,[7] while blood vessels are affected to a lesser extent compared to other ergot alkaloids.[1]

References

Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 5193–5. ISBN 978-3-85200-181-4.
Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 447. ISBN 3-8047-1763-2.
"Methergin". Fachinformation des Arzneimittel-Kompendium der Schweiz (in German).
Koehler PJ, Tfelt-Hansen PC (November 2008). "History of methysergide in migraine". Cephalalgia. 28 (11): 1126–35. doi:10.1111/j.1468-2982.2008.01648.x. PMID 18644039.
Niño-Maldonado AI, Caballero-García G, Mercado-Bochero W, Rico-Villademoros F, Calandre EP (November 2009). "Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study". Head & Face Medicine. 5 (21): 21. doi:10.1186/1746-160X-5-21. PMC 2780385. PMID 19895705.
"Methylergonovine Maleate Monograph for Professionals - Drugs.com". drugs.com. Archived from the original on 2016-09-20.
Pertz H, Eich E (1999). "Ergot alkaloids and their derivatives as ligands for serotoninergic, dopaminergic and adrenergic receptors". In Křen V, Cvak L (eds.). Ergot: the genus Claviceps. CRC Press. pp. 411–440. ISBN 978-905702375-0.

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[Austria-Codex-1] Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 5193–5. ISBN 978-3-85200-181-4.

[2] Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 447. ISBN 3-8047-1763-2.

[3] "Methergin". Fachinformation des Arzneimittel-Kompendium der Schweiz (in German).

[4] Koehler PJ, Tfelt-Hansen PC (November 2008). "History of methysergide in migraine". Cephalalgia. 28 (11): 1126–35. doi:10.1111/j.1468-2982.2008.01648.x. PMID 18644039.

[5] Niño-Maldonado AI, Caballero-García G, Mercado-Bochero W, Rico-Villademoros F, Calandre EP (November 2009). "Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study". Head & Face Medicine. 5 (21): 21. doi:10.1186/1746-160X-5-21. PMC 2780385. PMID 19895705.

[6] "Methylergonovine Maleate Monograph for Professionals - Drugs.com". drugs.com. Archived from the original on 2016-09-20.

[7] Pertz H, Eich E (1999). "Ergot alkaloids and their derivatives as ligands for serotoninergic, dopaminergic and adrenergic receptors". In Křen V, Cvak L (eds.). Ergot: the genus Claviceps. CRC Press. pp. 411–440. ISBN 978-905702375-0.