Dihydroergotamin

Breast Feeding; Lactation; Analgesics, Non-Narcotic; Dopamine Agonists; Vasoconstrictor Agents

Pharmaceuticals

Warning

H302 (66.7%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Treatment for ergotism consists of vasodilators, anticoagulants and low molecular weight dextrans. If necessary, a sympathetic nerve blockade may be carried out, such as brachial plexus blockade. Temporary sedation (e.g. haloperidol) will be necessary in hallucination and diazepam is used for convulsions. There is no specific antidote. (L1921, L1933)

N - Nervous system

QN - Nervous system

DHE is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. It is thought to exert its therapeutic effect through both neurological and vascular mechanisms. Its serotonin agonist activity may contribute to decreasing glutamatergic activity of the trigeminal system and subsequent cortical depolarization which is thought to participate in the neurological pathophysiology of migraine. The same serotonin agonist activity also contributes to vasoconstriction, producing both the characteristic side effect of chest tightness and potentially contributing to a therapeutic effect by counteracting the vasodilation due to calcitonin gene-related peptide (CGRP) release in migraine attacks.

DHE has several proposed mechanisms which may contribute to its therapeutic efficacy as an abortive therapy in migraines. Firstly, DHE's s agonist action on 5-hydroxytryptamine (5HT) 1b receptors in the smooth muscle of the cranial vasculature may provide relief via vasoconstriction of the blood vessels which typically become dilated due to the release of CGRP during migraine attacks. DHE's off-target action at alpha-adrenergic receptors may further contribute via this mechanism. The remaining mechanisms are thought to provide relief through the effects on the neurogenic causes of migraine symptoms. Agonist action by DHE on 5-HT_1b and 5-HT_1d receptors inhibits nociceptive signalling through the ventroposteromedial thalamus to the trigeminal sensory neurons. Further action on 5-HT_1b and 5-HT_1d receptors with the addition of agonist activity on 5-HT_1f in the trigeminal nucleus caudalis decreases afferent signalling to trigeminal sensory neurons which contributes to central sensitization. The success of experimental compounds selectively targetting the 5-HT_1f receptor lends support to this mechanism. Lastly, action at 5-HT_1d receptors on trigeminal nerve terminals inhibits the release of vasoactive neuropeptides thought to contribute to pain and inflammation during a migraine attack. DHE is known to have 10-fold less potency at the 5-HT_1b receptor than its predecessor ergotamine which reduces the incidence of vascular side effects. Notably, DHE slowly diffuses from receptors resulting in unreliable prediction of effects from plasma concentration.