methysergide

Action and Spectrum

Actions and Spectrum: 

Action: methysergide’s main action is to antagonize (block) specific serotonin receptors, particularly the 5-HT2A and 5-HT1D receptors. Doing so interferes with the effects of serotonin, a neurotransmitter that contributes to various physiological functions, including mood regulation, blood vessel constriction, and gastrointestinal function. The blocking of 5-HT2A receptors can impact hallucinogenic effects, while the blocking of 5-HT1D receptors is particularly relevant in migraines. 

Spectrum: 

Migraine Prevention: methysergide is most used for the prevention of severe migraines. By blocking the 5-HT1D receptors located on blood vessels, it helps to reduce the dilation of blood vessels in the brain that is associated with migraines. It can lead to a decrease in the frequency and intensity of migraine attacks. 

Drug Interaction

Adverse Reaction

Frequency not defined   

muscle or joint aches or discomfort 

weight gain 

a rash or facial flushing 

insomnia 

weakness or poor coordination 

drowsiness, dizziness, or lightheadedness 

diarrhea or constipation 

nausea, vomiting, heartburn, or abdominal pain 

Black Box Warning

Black Box Warning:  

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: methysergide should not be used in individuals who have shown hypersensitivity or allergic reactions to the medication or its components. 

Peripheral Vascular Disease: This medication can potentially worsen peripheral vascular disease, impacting blood vessels beyond the heart and brain. Administering methysergide to individuals with this ailment might result in reduced blood circulation and additional associated issues. 

Ischemic Heart Disease: methysergide can have vasoconstrictive effects, narrowing blood vessels. It could be problematic for individuals with ischemic heart disease, as it might further reduce blood flow to the heart muscle and potentially lead to angina or other cardiac complications. 

Uncontrolled Hypertension: Given its vasoconstrictive properties, methysergide may increase blood pressure. Using it in individuals with uncontrolled hypertension could worsen their condition and increase the risk of cardiovascular events. 

Renal or Hepatic Impairment: Impaired kidney or liver function can affect the metabolism and excretion of methysergide. It might result in higher concentrations of the medication within the body, consequently elevating the potential for experiencing adverse outcomes. 

Pregnancy and Breastfeeding: methysergide is generally not recommended during pregnancy due to concerns about its effects on fetal development. It may also pass into breast milk, posing a potential risk to nursing infants. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: X 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

methysergide is a medication that belongs to a class of drugs known as ergot alkaloids. It is primarily used for the preventive treatment of migraine headaches. 

Pharmacodynamics:  

methysergide acts as a partial agonist or antagonist at various serotonin receptors, including 5-HT1 and 5-HT2 receptors. Modulating serotonin receptor activity can influence the constriction of blood vessels and the transmission of pain signals,which are relevant to migraine headaches.  

Pharmacokinetics: 

Absorption 

methysergide is well-absorbed orally after administration. Food intake might influence its absorption, with higher absorption observed when taken on an empty stomach. Peak plasma concentrations are generally achieved within a few hours after oral ingestion. 

Distribution 

methysergide is extensively distributed throughout the body. It could traverse the blood-brain barrier, accessing the CNS, essential for its therapeutic effects. It is also distributed to various tissues and organs due to its lipophilic nature. 

Metabolism 

methysergide undergoes metabolism in the liver primarily through processes involving oxidative pathways, such as cytochrome P450 enzymes. The primary metabolites produced are hydroxylated derivatives. The metabolism of methysergide can vary among individuals due to genetic and environmental factors. 

Excretion and Elimination 

The excretion of methysergide and its metabolites occurs mainly through the renal route. The drug and its metabolites are expelled in the urine, with just a minor fraction being removed through bowel movements. The elimination half-life of methysergide can vary but generally falls within a few hours to around 12 hours. 

Adminstartion

Administration:  

methysergide is usually administered orally in the form of tablets or capsules. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: methysergide 

Why do we use methysergide?  

Migraine Headaches: methysergide has been used to help prevent the occurrence of migraine headaches, especially those that are frequent, severe, or resistant to other treatments. It works by constricting blood vessels and affecting specific brain receptors to reduce the frequency and intensity of migraines. 

Cluster Headaches: Cluster headaches are excruciating and occur in clusters over time. methysergide may be prescribed to prevent cluster headaches when other medications have not provided relief. The ability to constrict blood vessels and influence serotonin receptors contributes to its potential to reduce the occurrence and intensity of these episodes. 

Serotonin Receptor Modulation: methysergide primarily works by binding to serotonin receptors in the brain. Doing so modulates the effects of serotonin, a neurotransmitter that regulates mood, pain, and blood vessel constriction. This modulation helps in reducing headache symptoms.