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
Obstetrics is the field of study concentrated on pregnancy, childbirth and the postpartum period. As a medical specialty, obstetrics is combined with gynecology under the discipline known as obstetrics and gynecology (OB/GYN), which is a sur ...
and in the treatment of
migraine
Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...
. It reportedly produces
psychedelic
Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science o ...
effects similar to those of
lysergic acid diethylamide
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
(LSD) at high doses.
It is on the
World Health Organization's List of Essential Medicines.
Medical uses
Obstetric use
Methylergometrine is a smooth muscle constrictor that mostly acts on the
uterus
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
. 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 An active metabolite is an active form of a drug after it has been processed by the body.
Metabolites of drugs
An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...
of
methysergide.
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.
Contraindications
Methylergometrine is contraindicated in patients with
hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...
and
pre-eclampsia
Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...
.
It is also contraindicated in
HIV positive patients taking
protease inhibitors,
delavirdine
Delavirdine (DLV) (brand name Rescriptor) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) marketed by ViiV Healthcare. It is used as part of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency viru ...
, and
efavirenz
Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needle ...
(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
Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...
)
* Convulsions
In excessive doses, methylergometrine can also lead to cramping,
respiratory depression
Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapni ...
and coma.
Interactions
Methylergometrine likely interacts with drugs that inhibit the liver enzyme
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...
, such as
azole antifungal
An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryp ...
s,
macrolide antibiotic
The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Ma ...
s and many HIV drugs. It can also increase constriction of blood vessels caused by
sympathomimetic
Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in hea ...
drugs and other ergot alkaloids.
Pharmacology
Pharmacodynamics
Methylergometrine is an
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...
or
antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...
to
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...
,
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
, 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,
while blood vessels are affected to a lesser extent compared to other ergot alkaloids.
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.
Methylergometrine is a
synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to:
Science
* Synthetic chemical or compound, produced by the process of chemical synthesis
* Synthetic ...
analogue of
ergometrine, a
psychedelic
Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science o ...
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of simila ...
found in
ergot
Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''.
The most prominent member of this group is '' Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that c ...
, 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
Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science o ...
effects at doses of 2 mg and above.
This can be attributed to due to its agonistic action at the 5-HT
2A–
mGlu2 receptor
protomers. Clinical efficacy occurs around 200 µg, ten times lower than the hallucinogenic threshold.
Methylergometrine is an agonist of the serotonin 5-HT
2B receptor and has been associated with
cardiac valvulopathy.
Chemistry
Methylergometrine, also known as ''d''-lysergic acid 1-butanolamide, is a
derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...
of the
ergoline and
lysergamide classes and is structurally related to
ergometrine (''d''-lysergic acid β-propanolamide) and
lysergic acid diethylamide
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
.
References
{{Ergolines
Antimigraine drugs
Human drug metabolites
Lysergamides
Obstetric drugs
Serotonin receptor agonists