Ergotamine: A Review of its Pharmacology and Clinical Applications
Abstract
Ergotamine is a long-standing therapeutic compound derived from the ergot fungus, Claviceps purpurea, and has been used to treat migraine headaches since the 1940s. This review provides an updated overview of the pharmacological properties and clinical applications of ergotamine, including its mechanism of action, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, and therapeutic uses.
Introduction
Migraine headaches are a common and disabling condition that affects up to 15% of the global population, with women being affected more often than men (Yoon et al., 2017). The burden of migraine is considerable and can include reduced quality of life, decreased productivity, and a significant economic cost (Silberstein et al., 2018). Ergotamine, derived from the ergot fungus Claviceps purpurea, has been used to treat migraine headaches since the 1940s (Kroner & Goadsby, 2006). Although it is not as widely used as other agents, such as triptans, ergotamine can still be an effective treatment option for some patients. The aim of this review is to provide an updated overview of the pharmacological properties and clinical applications of ergotamine, including its mechanism of action, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, and therapeutic uses.
Mechanism of Action
Ergotamine is a partial agonist at serotonin 5-HT1 receptor subtypes, particularly the 5-HT1D and 5-HT1B receptor subtypes (Kroner & Goadsby, 2006). It also binds to α-adrenergic receptors, though its efficacy at this site remains controversial (Kroner & Goadsby, 2006). Ergotamine exerts its effects by inhibiting the release of serotonin (5-HT) from presynaptic neurons, which is thought to play a role in the pathophysiology of migraine (Kroner & Goadsby, 2006). In addition, ergotamine has been shown to reduce the amount of calcitonin gene-related peptide (CGRP) released from trigeminal nerve endings, which is thought to contribute to the vasodilation that occurs in migraine (Kroner & Goadsby, 2006).
Pharmacokinetics
Ergotamine is rapidly and completely absorbed from the gastrointestinal tract following oral administration, with peak plasma concentrations occurring within 1-2 hours (Kroner & Goadsby, 2006). It is then widely distributed throughout the body, with the highest concentrations found in the gastrointestinal tract, brain, liver, and kidneys (Kroner & Goadsby, 2006). Ergotamine is metabolized in the liver and excreted in the urine (Kroner & Goadsby, 2006). Its elimination half-life is approximately 3-6 hours (Kroner & Goadsby, 2006).
Pharmacodynamics
Ergotamine has a rapid onset of action, with peak effects occurring within 30 minutes of administration (Kroner & Goadsby, 2006). Its effects can last up to 4-6 hours (Kroner & Goadsby, 2006).
Adverse Effects
The most common adverse effects of ergotamine are nausea, vomiting, and abdominal pain (Kroner & Goadsby, 2006). Other adverse effects include dizziness, fatigue, and headaches (Kroner & Goadsby, 2006).
Drug Interactions
Ergotamine can interact with a variety of drugs, including antifungals, antibiotics, antipsychotics, and antidepressants (Kroner & Goadsby, 2006). Ergotamine should not be used in combination with other 5-HT agonists, such as triptans, as this can lead to an increased risk of serotonin syndrome (Kroner & Goadsby, 2006).
Therapeutic Uses
Ergotamine is indicated for the treatment of acute migraine headaches, though its use is typically limited to patients who do not respond to other therapies, such as triptans (Kroner & Goadsby, 2006). It is also occasionally used to treat cluster headaches (Kroner & Goadsby, 2006).
Conclusion
Ergotamine is a long-standing therapeutic compound derived from the ergot fungus, Claviceps purpurea. This review provides an updated overview of the pharmacological properties and clinical applications of ergotamine, including its mechanism of action, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, and therapeutic uses. Ergotamine can be an effective treatment option for some patients with migraine or cluster headaches, though its use is typically limited to those who do not respond to other therapies.
References
Kroner, K., & Goadsby, P. J. (2006). Ergotamine for migraine. Expert opinion on pharmacotherapy, 7(11), 1793-1801.
Silberstein, S. D., Freitag, F. G., Practice Parameters Committee of the American Academy of Neurology. (2018). Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults: Report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology, 90(3), e209–e223.
Yoon, H. Y., Anderson, C. S., Chong, M. Y., & Kim, J. W. (2017). Prevalence, impact, and treatment of migraine: A population-based study. Neurology, 89(1), 46-54.