metergoline

Action and Spectrum

Actions and Spectrum: 

metergoline is a psychoactive drug used for various medical purposes, including the therapy of migraines and Parkinson’s disease. It acts primarily as a serotonin receptor antagonist, affecting different subtypes of serotonin receptors in the brain.  

Action: metergoline exerts its effects by interacting with serotonin receptors, which are part of the broader class of G protein-coupled receptors. It acts as an antagonist at several serotonin receptor subtypes, which blocks the binding of serotonin (a neurotransmitter) to these receptors, thereby altering serotonin-mediated signaling in the brain. 

Spectrum: metergoline’s spectrum of action covers various serotonin receptor subtypes, and its effects can be broad due to its interactions with these receptors. It has been investigated and used for several medical conditions, including: 

• Migraine: Due to its antagonism of 5-HT1D and 5-HT1B receptors, metergoline was explored as a potential treatment for migraines. These receptors plays a key role in regulating blood vessels, and their dysfunction is associated with migraine attacks. 
• Parkinson’s Disease: Some studies explored metergoline’s potential in treating Parkinson’s disease, but this use has not been widely adopted. The rationale behind this application lies in its interactions with serotonin receptors involved in movement regulation. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Nausea 

Weakness 

Vomiting 

Drowsiness 

Anxiety  

Insomnia 

Dizziness 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: Individuals with a known hypersensitivity or allergic reaction to metergoline or related compounds should not use this medication. 
• Serotonergic Syndrome Risk: metergoline’s action on serotonin receptors could potentially contribute to the risk of serotonin syndrome. Serotonin syndrome generally is a potentially life-threatening condition resulting from excessive brain and body serotonin activity.  
• Cardiovascular Conditions: metergoline may impact blood vessels due to its action on serotonin receptors involved in vasoconstriction. Individuals with certain cardiovascular conditions, such as coronary artery disease or those at risk of cardiac events, may be advised against using metergoline. 
• Liver Impairment: Since metergoline is metabolized in the liver, individuals with significant liver impairment or disease may experience altered metabolism and potential drug accumulation. Dose adjustments or avoidance may be necessary in such cases. 
• Renal Impairment: While the primary elimination route of metergoline is hepatic (via the liver), individuals with severe renal impairment may require cautious use or dose adjustments. 
• Pregnancy and Breastfeeding: The safety of metergoline during pregnancy and breastfeeding has not been well established. 
• Interactions: metergoline can interact with various medications, particularly those that affect serotonin signaling. Combining metergoline with other serotonergic drugs could increase the risk of serotonin syndrome. Additionally, it may interact with medications metabolized by the liver’s cytochrome P450 enzymes. 
• Psychiatric Conditions: Since metergoline can impact serotonin receptors associated with mood regulation, caution is advised when using this medication in individuals with psychiatric conditions, such as depression or anxiety. 
• Age and Pediatric Use: The use of metergoline in pediatric populations is limited, and caution is advised due to potential impacts on development and serotonin regulation. 
• Elderly Population: Elderly individuals may be more susceptible to adverse effects of metergoline due to age-related changes in drug metabolism and receptor sensitivity. 

Caution 

• Serotonin Syndrome: metergoline’s interactions with serotonin receptors can enhance the risk of serotonin syndrome, a potentially life-threatening condition characterized by symptoms such as confusion, agitation, rapid heart rate, elevated blood pressure, dilated pupils, muscle rigidity, and, in severe cases, seizures. Caution is needed when using metergoline alongside other medications that affect serotonin levels, like certain antidepressants (e.g., SSRIs, SNRIs). 
• Cardiovascular Effects: metergoline’s impact on serotonin receptors involved in blood vessel regulation may affect cardiovascular function. Individuals with a history of cardiovascular conditions, including heart disease, should be closely monitored using metergoline, as it could impact blood pressure and heart rate. 
• Interactions: metergoline can interact with other medications, particularly those metabolized by the liver’s cytochrome P450 enzymes. To avoid potential interactions, you must inform your healthcare provider about all your medications. 
• Liver and Kidney Function: metergoline is metabolized by the liver, and its use might need to be adjusted or avoided in individuals with liver impairment. Although its primary elimination route is hepatic, individuals with severe kidney impairment should also be cautious when using metergoline. 
• Pregnancy and Breastfeeding: The safety of metergoline during pregnancy and breastfeeding has not been well established. Due to its potential effects on serotonin receptors and the developing fetus or newborn, caution is advised, and its use during these periods should be discussed with a healthcare professional. 
• Mental Health: As metergoline affects serotonin receptors linked to mood regulation, individuals with a history of psychiatric conditions, such as depression or anxiety, should be cautious when using this medication. Changes in mood or exacerbation of existing psychiatric symptoms could occur. 
• Elderly Population: Elderly individuals may be more vulnerable to adverse effects of metergoline due to age-related changes in drug metabolism and receptor sensitivity. Dose adjustments and close monitoring may be necessary. 
• Pediatric Use: The use of metergoline in pediatric populations is limited, and caution is advised due to potential impacts on development and serotonin regulation. 
• Driving and Operating Machinery: metergoline may affect cognition, alertness, and coordination. Individuals taking this medication should be cautious when driving, operating heavy machinery/engaging in activities that require mental alertness. 
• Withdrawal: Abruptly discontinuing metergoline may lead to withdrawal symptoms due to changes in serotonin receptor activity. Tapering the dose under medical supervision is recommended if discontinuing the medication. 
• Individual Variation: People may respond differently to metergoline due to genetic, physiological, and environmental factors. Close monitoring and personalized adjustments may be needed based on individual responses. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• 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: 

metergoline is a psychoactive compound with pharmacological actions primarily mediated by its interactions with various serotonin receptors in the central nervous system. As a mixed serotonin receptor antagonist and partial agonist, metergoline targets receptors such as 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, and 5-HT7, influencing serotoninergic neurotransmission.

By modulating these receptors, metergoline affects neurotransmitter signaling pathways involved in mood regulation, pain perception, vasoconstriction, and motor control. While its historical uses included migraine prevention, Parkinson’s disease treatment, and psychiatric disorder modulation, its limited selectivity and potential for adverse effects have led to a decline in its therapeutic use over time. 

Pharmacodynamics: 

Mechanism of action: metergoline’s mechanism of action involves its interactions with various serotonin (5-HT) receptors in the central nervous system. It acts as a mixed agonist and antagonist at different serotonin receptor subtypes, influencing serotoninergic neurotransmission and affecting various physiological processes.  

• Serotonin Receptors: metergoline targets different subtypes of serotonin receptors, which are generally a part of the G protein-coupled receptor family. These receptors are crucial in regulating neurotransmitter signaling in the brain and are involved in mood, cognition, pain perception, and other physiological processes. 
• Partial Agonist and Antagonist: metergoline can act as a partial agonist and an antagonist at different serotonin receptor subtypes. As a partial agonist, it can activate receptors to a certain extent, and as an antagonist, it can block the binding of serotonin or other agonists to the receptors. 
• 5-HT1A Subtype: At the 5-HT1A receptor subtype, metergoline acts as a partial agonist. This receptor is involved in mood regulation, anxiety reduction, and other processes. 
• 5-HT1B and 5-HT1D Subtypes: metergoline is an antagonist at both the 5-HT1B and 5-HT1D receptor subtypes. These receptors are involved in vasoconstriction and are targeted for treating migraines. By blocking these receptors, metergoline aims to reduce migraine symptoms. 
• 5-HT2A, 5-HT2C, and 5-HT7 Subtypes: metergoline is an antagonist in these receptor subtypes. The 5-HT2A receptor is associated with mood regulation, perception, and hallucinogenic effects. The 5-HT2C receptor is linked to appetite regulation, mood, and anxiety. The 5-HT7 receptor is involved in mood regulation and cognitive processes. 
• Central Nervous System Effects: metergoline can modulate serotonin signaling pathways in the brain through its interactions with these various receptor subtypes. This modulation can influence mood, pain perception, movement, and other physiological processes. 

Pharmacokinetics: 

Absorption 

metergoline is typically administered orally in the form of tablets. After oral administration, it is absorbed from the gastrointestinal tract into the bloodstream. The rate and extent of absorption may be influenced by factors such as the formulation of the medication and individual patient characteristics. 

Distribution 

Once absorbed into the bloodstream, metergoline will likely be distributed throughout the body. Due to its psychoactive effects, it could cross the blood-brain barrier and interact with serotonin receptors in the central nervous system. The extent of distribution to various tissues and organs and its binding to plasma proteins may impact its overall effects and duration of action. 

Metabolism 

metergoline is expected to undergo metabolism in the liver, primarily through enzymatic processes involving cytochrome P450 enzymes. The specific metabolites that result from this metabolism can influence the drug’s overall pharmacological activity, efficacy, and safety. The details of metergoline’s specific metabolic pathways and metabolites might need to be better characterized. 

Elimination and Excretion 

Metabolized products of metergoline, along with any unchanged drug, are excreted from the body. This excretion occurs mainly through the kidneys in the form of urine. The elimination half-life of metergoline, which is the time it takes for half of the drug to be cleared from the body, can vary based on factors such as metabolism and excretion rates. 

Adminstartion

Administration: 

A healthcare professional should always guide the administration of metergoline, and it’s essential to follow their instructions and the medication’s prescription label. metergoline is usually available in the form of oral tablets.  

• Dosage: The appropriate dosage of metergoline varies depending on the medical condition being treated, the patient’s age, weight, and also overall health, as well as other factors. Your healthcare provider will determine the dosage. 
• Timing: metergoline is typically taken orally with or without food, as directed by your doctor. The dosing frequency can vary; it might be taken once daily or divided into multiple daily doses. Always follow your doctor’s instructions on when and how to take the medication. 
• Consistency: Taking metergoline consistently as your healthcare provider prescribes is essential. Skipping doses or changing the dosing schedule without medical approval can affect the effectiveness of the treatment. 
• Duration of Use: The duration of treatment with metergoline varies depending on the medical condition being treated. Some conditions may require short-term use, while others might involve longer-term therapy. Always follow your doctor’s recommendations regarding the duration of treatment. 
• Adjustments and Discontinuation: Do not adjust the dosage or discontinue the drug without consulting your healthcare provider. Abruptly stopping metergoline can lead to withdrawal symptoms and potential adverse effects. 
• Monitoring: Regular check-ups and medical appointments are essential while taking metergoline. Your doctor will monitor the response to the medication and make any necessary adjustments to your therapy plan. 
• Special Populations: Dosage adjustments might be necessary for individuals with certain medical conditions, like liver or kidney impairment, and in elderly or pediatric populations. Always follow your doctor’s guidance in these cases. 
• Missed Dose: If you miss a dose, take it as soon as you remember. However, if it’s close to the time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: metergoline 

Why do we use metergoline? 

metergoline has been used for various medical purposes, but it has become less common over time because of safety concerns and the availability of alternative treatments.  

• Hyperprolactinaemia: metergoline is a serotonin receptor antagonist that was used for various medical purposes, including the treatment of hyperprolactinemia, a condition characterized by elevated levels of the hormone prolactin in blood. Prolactin is primarily known for its role in stimulating milk production in breastfeeding individuals, but it also has other functions in the body. 
• Migraine Prevention: metergoline has been investigated for its potential to prevent migraines. It primarily acts as an antagonist at serotonin receptors, particularly 5-HT1D and 5-HT1B receptors, which regulate blood vessel constriction. metergoline aims to reduce the frequency and severity of migraines by affecting these receptors. 
• Parkinson’s Disease: Studies have explored the use of metergoline as a treatment for Parkinson’s disease. metergoline’s interaction with serotonin receptors was thought to benefit motor function and movement control. However, other medications with more established efficacy and safety profiles are typically preferred for treating Parkinson’s disease. 
• Psychiatric Disorders: Due to its impact on serotonin receptors, metergoline has been studied for its potential effects on psychiatric disorders such as depression and anxiety. However, its use in this context has been limited, and more established medications are available for these conditions. 
• Cluster Headaches: Cluster headaches are severe and challenging to treat. Some studies have explored the use of metergoline for cluster headache prevention due to its impact on serotonin receptors involved in pain modulation. 
• Menstrual Disorders: There have been investigations into using metergoline to treat certain menstrual disorders, such as premenstrual syndrome (PMS). Its effects on serotonin receptors were thought to potentially alleviate the emotional and physical symptoms associated with PMS.