Ergotamine and Dihydroergotamine: History, Pharmacology, and Efficacy

Abstract

Ergotamine and dihydroergotamine share structural similarities with the adrenergic, dopaminergic, and serotonergic neurotransmitters. As a result, they have wide-ranging effects on the physiologic processes that they mediate. Ergotamine and dihydroergotamine are highly potent at the 5-HT1B and 5-HT1D antimigraine receptors and, as a consequence, the plasma concentrations that are necessary to produce the appropriate therapeutic and physiologic effects are very low. The broad spectrum of activity at other monoamine receptors is responsible for their side effect profile (dysphoria, nausea, emesis, unnecessary vascular effects). Both ergotamine and dihydroergotamine have sustained vasoconstrictor actions. In acute migraine treatment, their mechanisms of action involve constricting the pain-producing intracranial extracerebral blood vessels at the 5-HT1B receptors and inhibiting the trigeminal neurotransmission at the peripheral and central 5-HT1D receptors. The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine. Their wide use is based on long-term experience.

Serotonergic Agents in the Management of Cluster Headache

“…This structural modification is believed to be responsible for the differences between the pharmacokinetic, pharmacodynamic, and adverse event profiles of DHE and ET [11]. ET and DHE have a high affinity for the 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 1F , 5-HT 2A , 5-HT 2C , and 5-HT 4 receptor subtypes, as well as for various adrenergic receptors in blood vessels and various smooth muscles and dopaminergic receptors [12]. The vasoconstrictor activity of these ergot alkaloids initially was thought to be their mode of action in head pain, although other possible mechanisms for the beneficial effect of ergot alkaloids now are considered more likely, including an effect on neurogenic inflammation [13] and an action on central serotonergic neurons [14].…”

“…Adverse events Ergotamine's side-effect profile reflects its agonist activity at the 5-HT 1A (nausea, dysphoria), 5-HT 2A (peripheral vasoconstriction), and dopamine D 2 (nausea, vomiting) receptors [12]. It is therefore contraindicated in patients with coronary or peripheral vascular disease, arterial hypertension, and severe liver and kidney disease.…”

Goshuyuto, a Traditional Japanese Medicine, and Aqueous Extracts of Evodiae Fructus Constrict Isolated Rat Aorta via Adrenergic and/or Serotonergic Receptors

“…13,26) The present study elucidated that goshuyuto constricted isolated rat aorta. Goshuyuto may relieve migraine by constricting the relaxed blood vessels like sumatriptan and ergotamine.…”

Acute pharmacotherapy of migraine, tension-type headache, and cluster headache

“…Ergotamine [23,24] is not the drug of first choice for the treatment of migraine attacks. It has an effect on the 5-HT1B/1D receptor but also an effect on 5-HT2A (results in general vasoconstriction) and dopamine D2 receptor (can result in nausea/vomiting) [25].…”

“…Similarly, DHE is less emetic than ergotamine (dopamine D2) [23]. DHE can be used parenterally [30] or by the nasal route [23,24] in the treatment of migraine attacks. For adverse potential events of DHE, see ref.…”