Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and as an antimigraine agent in the treatment of migraine . It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.
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.
Migraine
Methylergometrine is sometimes used for both prevention
and acute treatment
of migraine. It is an active metabolite of
methysergide.
In the treatment of
, 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.
Contraindications
Methylergometrine is contraindicated in patients with
hypertension and
pre-eclampsia.
It is also contraindicated in
HIV positive patients taking protease inhibitors,
delavirdine, and
efavirenz (which is also an agonist at the 5-HT
2A–mGlu2 receptor protomer and increases the chances of a patient experiencing hallucinations during methylergometrine therapy).
Side effects
Adverse effects include:
-
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.
Interactions
Methylergometrine likely interacts with drugs that inhibit the liver enzyme CYP3A4, such as
, macrolide antibiotics and many HIV drugs. It can also increase constriction of blood vessels caused by
sympathomimetic drugs and other ergot alkaloids.
Pharmacology
Pharmacodynamics
+
! 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 | ? | Agonist |
| 5-HT2C | 4.6–43.7 | ? | Full agonist |
| 5-HT3 | ? | – | – |
| 5-HT5A | ? | 24.4 | Full agonist |
| 5-HT6 | ? | ? | Full agonist |
| 5-HT7 | 11–52 | ? | Full agonist |
Notes: All sites are human except 5-HT1B (rat) and 5-HT7 (guinea pig). Refs: |
Methylergometrine is an partial agonist or antagonist to serotonin, dopamine, and α-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 serotonin 5-HT2A receptors,
Pharmacokinetics
The
bioavailability of methylergometrine is 60% via oral administration and 78% by intramuscular injection.
It is
drug metabolism in the
liver, with extensive first-pass metabolism.
The elimination half-life of the drug is 3.4hours.
It is eliminated mainly via metabolism and then
excretion.
Natural occurrence
Previously thought to be an exclusively synthetic compound, it has been reported to occur
natural product in
Argyreia nervosa (Hawaiian baby woodrose).
The drug is on the World Health Organization's List of Essential Medicines.
Chemistry
Methylergometrine, also known as
d-lysergic acid 1-butanolamide, is a derivative of the
ergoline and
lysergamide classes and is structurally related to
ergometrine (
d-lysergic acid β-propanolamide) and lysergic acid diethylamide (LSD).
History
Methylergometrine was first described in the scientific literature by 1945.
Society and culture
Recreational use
Methylergometrine is a synthetic analogue of
ergometrine, a
Psychedelic drug alkaloid found in
ergot, and many species of
morning glory. Methylergometrine is a member of the
ergoline family and chemically similar to
LSD,
ergine,
ergometrine, and
lysergic acid. According to
Jonathan Ott, methylergometrine produces LSD-like
psychedelic effects at doses of 2 mg and above.
Clinical effectiveness of methylergometrine as a medication occurs around 200μg, which is 10times lower than the hallucinogenic threshold.
See also
External links
