Methylergometrine

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Methylergometrine
Clinical data
Trade namesMethergine
Other namesMethylergonovine; methylergobasin; Methylergobasine; Methylergobrevin; d-Lysergic acid 1-butanolamide; N-[(2S)-1-Hydroxybutan-2-yl]-6-methyl-9,10-didehydroergoline-8β-carboxamide
AHFS/Drugs.comInternational Drug Names
MedlinePlusa601077
Pregnancy
category
  • Contraindicated
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
MetabolismLiver
Elimination half-life30–120 minutes
ExcretionMostly bile
Identifiers
  • (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
JSmol)
Melting point172 °C (342 °F)
Solubility in waterInsoluble mg/mL (20 °C)
  • CC[C@@H](CO)NC(=O)[C@@H]2/C=C1/c3cccc4N\C=C(\C[C@H]1N(C)C2)c34
  • 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 ☒N
  • Key:UNBRKDKAWYKMIV-QWQRMKEZSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the

lysergic acid diethylamide (LSD) at high doses.[citation needed
]

It is on the World Health Organization's List of Essential Medicines.[1]

Medical 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.[2][3][4]

Migraine

Methylergometrine is sometimes used for both prevention[5] and acute treatment[6] of migraine. It is an active metabolite of methysergide.[7] In the treatment of cluster headaches, methylergometrine has been initiated at a dose of 0.2 mg/day, rapidly increased to 0.2 mg three times per day, and increased to a maximum of 0.4 mg three times per day.[7]

Contraindications

Methylergometrine is contraindicated in patients with

protease inhibitors, delavirdine, and efavirenz (which is also an agonist at the 5-HT2A–mGlu2 receptor protomer and increases the chances of a patient experiencing hallucinations during methylergometrine therapy).[8]

Side effects

Adverse effects include:[2]

  • Nausea, vomiting, and diarrhea
  • Dizziness
  • Pulmonary hypertension[citation needed]
  • 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.[2]

Interactions

Methylergometrine likely interacts with drugs that inhibit the liver enzyme

sympathomimetic drugs and other ergot alkaloids.[2]

Pharmacology

Pharmacodynamics

Methylergometrine is an

5-HT2A receptors,[9] while blood vessels are affected to a lesser extent compared to other ergot alkaloids.[2] It has been found to interact with the serotonin 5-HT1A, 5-HT1B, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, and 5-HT7 receptors.[10][11][12][13]

Methylergometrine is a

protomers.[citation needed] Clinical efficacy occurs around 200 µg, ten times lower than the hallucinogenic threshold.[14]

Methylergometrine is an agonist of the serotonin 5-HT2B receptor and is maybe linked to

cardiac valvulopathy.[15]

Activities of methylergometrine at various sites[10][11][16][17][12][18][19]
Site Affinity (Ki [nM]) Efficacy (Emax [%]) Action
5-HT1A 1.5–2.0 ? Full agonist
5-HT1B 251 ? Full agonist
5-HT1D 0.86–2.9 70 Partial agonist
5-HT1E 89 ? Full agonist
5-HT1F 31 ? Full agonist
5-HT2A 0.35–1.1 ? Full agonist
5-HT2B 0.46–2.2 ? Full or partial agonist
5-HT2C 4.6–43.7 ? Full agonist
5-HT3 ? – –
5-HT5A ? 24.4[13] Full agonist[13]
5-HT6 ? ? Full agonist
5-HT7 11–52 ? Full agonist
Notes: All sites are human except 5-HT1B (rat) and 5-HT7 (guinea pig).[10][11]

Chemistry

Methylergometrine, also known as d-lysergic acid 1-butanolamide, is a

lysergic acid diethylamide
.

References

  1. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  2. ^
    ISBN 978-3-85200-181-4
    .
  3. ISBN 3-8047-1763-2
    .
  4. ^ "Methergin". Fachinformation des Arzneimittel-Kompendium der Schweiz (in German).[permanent dead link]
  5. S2CID 22433355
    .
  6. PMID 19895705
    .
  7. ^
    S2CID 34063682
    .
  8. ^ "Methylergonovine Maleate Monograph for Professionals - Drugs.com". drugs.com. Archived from the original on 2016-09-20.
  9. ISBN 978-905702375-0
    .
  10. ^ a b c "PDSP Database - UNC". pdsp.unc.edu. Archived from the original on 16 April 2021. Retrieved 15 January 2022.
  11. ^ a b c "PDSP Database - UNC". pdsp.unc.edu. Archived from the original on 16 April 2021. Retrieved 15 January 2022.
  12. ^
    ISBN 978-0-08-054111-2
    .
  13. ^
    PMID 35835867
    .
  14. ^
    PMID 7420432
    .
  15. PMID 24361689
    .
  16. PMID 11104741
    .
  17. S2CID 266103427
    . 2663.
  18. ISBN 978-1-4200-0113-6
    .
  19. ISBN 9780429219764. Archived from the original
    (PDF) on 2021-04-16.