Dihydroergotamine, Ergotamine, Methysergide and Sumatriptan – Basic Science in Relation to Migraine Treatment

  title={Dihydroergotamine, Ergotamine, Methysergide and Sumatriptan – Basic Science in Relation to Migraine Treatment},
  author={Carl G. H. Dahl{\"o}f and Antoinette Maassen van den Brink},
  journal={Headache: The Journal of Head and Face Pain},
The 5‐hydroxytryptamine (5‐HT) receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5‐HT1B, 5‐HT1D, and 5‐HT1F receptors. Ergotamine, dihydroergotamine, and methysergide, as well as the “triptan” sumatriptan, are all agonists for these receptors. The receptor profile and degree of selectivity of these four drugs differ, which is reflected by their side effects that limit their use in the acute and prophylactic treatment of migraine. The… 

Dihydroergotamine (DHE) – Is there a place for its use?

Most clinical data confirm that the drug is still an important element of contemporary migraine therapy, especially in cases when conventional medicine fails, and its role in modern therapy based on available clinical trials is confirmed.

Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs

Although the triptans are very effective in treating migraine attacks, their shortcomings have stimulated the search for novel drugs, and the focus is on 5-HT1F receptor agonists, which seem devoid of vascular side effects.

Dihydroergotamine: A Review of Formulation Approaches For the Acute Treatment of Migraine

Among parenteral formulations (including subcutaneous, intramuscular, intravenous and nasal spray), efficacy is superior with injectable dosing, but there are no head-to-head comparisons with triptans available for review.

The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse

The acute treatment of migraine will certainly improve with the advent of two novel classes of drugs, i.e., the 5-HT1F receptor agonists (lasmiditan) and the small molecule CGRP receptor antagonists (gepants).

Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine attacks. A review of new drugs and new administration forms of established drugs

None of these reviewed treatments are likely to fulfill patients' expectations, and the advancement of acute migraine drugs should likely depend on different mechanisms from current 5-HT-related drugs.

Side effects associated with current and prospective antimigraine pharmacotherapies

This review considers the adverse (or potential) side effects produced by current and prospective antimigraine drugs, including medication overuse headache (MOH) produced by ergots and triptans, the side effects observed in clinical trials for the new gepants and CGRP antibodies, and a section discussing the potential effects resulting from disruption of the cardiovascular CGRPergic neurotransmission.

An outlook on the trigeminovascular mechanisms of action and side effects concerns of some potential neuropeptidergic antimigraine therapies

The present review summarizes the current knowledge on the role of the above neuropeptides in the trigeminovascular system, and migraine pathophysiology, and discusses some issues related with the mechanisms of action and side effects concerns that could be elicited when targeting the CGRPergic, PACAPergic, oxytocinergic and orexinergic systems.

Potential risk of dihydroergotamine causing medication- overuse headache: preclinical evidence

It is demonstrated that chronic DHE administration can increase cortical excitability and increase c-Fos expression in caudal brainstem and the possible adverse effect of chronic D HE use in causing chronification of headache is suggested.

Relatively slow and long-lasting antimigraine effect of dihydroergotamine is most likely due to basic pharmacological attributes of the drug: A review

  • P. Tfelt-Hansen
  • Medicine
    Cephalalgia : an international journal of headache
  • 2013
DHE has a slow dissociation from the receptor; and this basic attribute of the drug is the most likely cause of the general relatively slow anti-migraine effect of DHE.



SUMATRIPTAN: a receptor-targeted treatment for migraine.

Clinical data indicate that sumatriptan relieves headache, nausea, and photophobia in a majority of acute migraine patients, and it possesses favorable side effect and safety profiles.

Ergotamine and Dihydroergotamine: History, Pharmacology, and Efficacy

The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine, and their wide use is based on long‐term experience.

Pharmacology of Dihydroergotamine and Evidence for Efficacy and Safety in Migraine

DHE is a significantly less potent arterioconstrictor than isET, which makes it a potentially much safer drug, and is associated with a markedly lower incidence of medication‐withdrawal headache, nausea, and vomiting than is ET.

The pharmacology of ergotamine and dihydroergotamine.

Intranasal administration of DHE delivers adequate plasma concentrations of the drug without the need for parenteral administration and should further expand its role in migraine pharmacotherapy.

Sumatriptan: Pharmacological Basis and Clinical Results

  • C. Dahlöf
  • Medicine
    Current medical research and opinion
  • 2001
All triptans appear to be very similar with respect to efficacy and tolerability as well as safety in clinical practice, in particular after dose adjustments have been made.

Pharmacology of antimigraine drugs

The selectivity of the pharmacological effects of these antimigraine drugs strongly suggests that excessive dilatation in the extracerebral cranial vasculature, probably initiated by a neuronal event, is an integral part of the pathophysiology of migraine.

5-Hydroxytryptamine and the pathophysiology of migraine

There seems convincing evidence that central release of 5-HT by various drug mechanisms causes migraine-like headache in migraineurs, but it remains to be seen whether these drugs mimic the pathological event initiating the spontaneous migraine attack.

Safety and Efficiency of Ergotamine Tartrate and Dihydroergotamine in the Treatment of Migraine and Status Migrainosus.

The background information for the Practice Parameter is provided, and the appropriate use of ergotamine tartrate and DHE in the treatment of (1) migraine and (2) status migrainosus is defined.

Effects of 5-Hydroxytryptamine and Ergotamine on Human Superficial Temporal Artery

Isometric tension was recorded in ring preparations of human superficial temporal arteries contracted by noradrenaline, 5-hydroxytryptamine, and ergotamine, revealing both a vasoconstrictive and a 5-HT-blocking activity.

Integrating the triptans into clinical practice

  • C. Dahlöf
  • Medicine, Psychology
    Current opinion in neurology
  • 2002
The triptans are becoming the first‐line alternatives in the acute pharmacological treatment of migraine, at least for attacks of moderate‐to‐severe intensity, and the tablet is the most commonly used triptan formulation.