Sustained pain relief with dihydroergotamine in migraine is potentially due to persistent binding to 5-HT1B and 5-HT1D receptors

@article{Kori2013SustainedPR,
  title={Sustained pain relief with dihydroergotamine in migraine is potentially due to persistent binding to 5-HT1B and 5-HT1D receptors},
  author={Shashidar H. Kori and J Zhang and Donald J. Kellerman and Thomas Alex Armer and Peter J. Goadsby},
  journal={The Journal of Headache and Pain},
  year={2013},
  volume={14},
  pages={P75 - P75}
}
Several studies show that dihydroergotamine (DHE) produces sustained migraine pain relief, measured up to 48 hours, although its serum half-life is only 10-13 hours. The extended duration of action has been attributed to an active metabolite (8’-OH-DHE) with a much longer half-life than the parent compound. However, recent pharmacokinetic studies demonstrate that DHE metabolites measured in humans are too low to have substantial clinical effect and probably do not contribute to sustained… 
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
TLDR
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.
Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine attacks. A review of new drugs and new administration forms of established drugs
TLDR
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.
Orally Inhaled Dihydroergotamine: A Review
TLDR
Inhalable DHE provides the promise of a new formulation of a valued medication with important clinical features, useful deep into attacks in a variety of situations.
Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect
TLDR
A general delay of effect in oral antimigraine drugs is strongly indicated and is likely that a complex antimigraines system with more than 1 site of action is involved.
Inhaled drug therapy development for the treatment of migraine
TLDR
Inhaled DHE offers rapid absorption with a pharmacokinetic profile similar to IV administration and will likely provide a good alternative to patients seeking rapid relief without the need for injection or other invasive routes.
Acute Reversible Cerebral Vasoconstriction Syndrome With Low-Dose Dihydroergotamine Possibly Potentiated by Valproic Acid and Erenumab: A Case Report
TLDR
A 64-year-old woman with chronic migraine and medication-overuse headache was electively admitted for 5 days of intravenous ketamine to treat intractable migraine pain and showed confluent bilateral T2 hyperintensities with punctate restricted diffusion in the occipital lobes associated with multi-segmental narrowing consistent with RCVS.
Pharmacological strategies to treat attacks of episodic migraine in adults
TLDR
Investigations into the mechanisms of the delay should have a high priority, both in studies with animals, migraine models, and in migraine patients during attacks, as they possibly also can increase Emax.
Triptans and ergot alkaloids in the acute treatment of migraine: similarities and differences
TLDR
In three comparative, randomized controlled trials (RCTs), oral triptans were superior to oral ergotamine 2 mg plus caffeine 200 mg for headache relief (HR) and two other RCTs demonstrated that ergot alkaloids can be equipotent [7] or superior [8] to a triptan.
Naratriptan is as effective as sumatriptan for the treatment of migraine attacks when used properly. A mini-review
  • P. Tfelt-Hansen
  • Medicine
    Cephalalgia : an international journal of headache
  • 2021
TLDR
Naratriptan was marketed for the treatment of migraine attacks as the “gentle triptan” in a low oral dose of 2.5 mg, a dose with no more adverse events than placebo, but in high doses oral nar atriptan is similar to oral sumatriptans.
Advances in Drug Development for Acute Migraine
TLDR
Future acute treatment needs, drugs in development for acute migraine, and new products that deliver established drugs to improve treatment response are explored.
...
...

References

SHOWING 1-2 OF 2 REFERENCES
Lack of drug interaction between the migraine drug MAP0004 (orally inhaled dihydroergotamine) and a CYP3A4 inhibitor in humans
TLDR
It is demonstrated that CYP3A4 inhibition had little to no effect on DHE PK after MAP0004 administration, apparently because of its high systemic and low gastrointestinal bioavailability.