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

  title={Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs},
  author={Martha B. Ram{\'i}rez Rosas and Sieneke Labruijere and Carlos M. Villal{\'o}n and Antoinette Maassen VanDenBrink},
  journal={Expert Opinion on Pharmacotherapy},
  pages={1599 - 1610}
Introduction: The introduction of the triptans (5-hydroxytryptamine (5-HT)1B/1D receptor agonists) was a great improvement in the acute treatment of migraine. However, shortcomings of the triptans have prompted research on novel serotonergic targets for the treatment of migraine. Areas covered: In this review the different types of antimigraine drugs acting at 5-HT receptors, their discovery and development are discussed. The first specific antimigraine drugs were the ergot alkaloids… 

Serotonin receptor targeted therapy for migraine treatment: an overview of drugs in phase I and II clinical development

The 5-HT1F receptor agonist lasmiditan, a drug acting through non-vasoconstrictive mechanisms, represents a promising safe, effective and tolerated acute migraine therapy also for patients at cardiovascular risk.

Outlining migrainous through dihydroergotamine–serotonin receptor interactions using quantum biochemistry

Since the early days of migrainous research, serotonin receptors (5-HTR) have been considered a major target of drugs, and the 5-HT1B and 5-HT1D agonists have been among the most marketed ones for

Targeted 5-HT1F Therapies for Migraine

Although ongoing phase III clinical trials are needed to confirm its efficacy and safety, lasmiditan might offer an alternative to treat acute migraine with no associated cardiovascular risk.

Structure and function of serotonin G protein-coupled receptors.

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.

Beyond its anti‐migraine properties, sumatriptan is an anti‐inflammatory agent: A systematic review

The literature review indicates that at low doses, sumatriptan can reduce inflammatory markers (e.g., interleukin‐1β, tumor necrosis factor‐α, and nuclear factor‐κB), affects caspases and changes cells lifespan, andNitric oxide synthase and nitric oxide signaling seem to be regulated by this drug.

Ergot Alkaloids (Re)generate New Leads as Antiparasitics

The ergot alkaloid scaffold is identified as a promising structural framework for designing potent agents targeting parasitic bioaminergic G protein coupled receptors, while serotonergic antagonists phenocopied PZQ action are identified.

A Dynamic View of Molecular Switch Behavior at Serotonin Receptors: Implications for Functional Selectivity

This work applies classical molecular dynamics simulations and enhanced sampling approaches to analyze the behavior of specific residues in the X-ray crystal structure of serotonergic 5-HT2B receptors to underpin the structural basis of functional selectivity.

Hejie Zhitong prescription promotes sleep and inhibits nociceptive transmission-associated neurotransmitter activity in a rodent migraine model

HJZT exerts a synergistic effect with pentobarbital sodium on promoting sleep and inhibits the expression of nociceptive transmission-associated neurotransmitters, including 5-HT, CGRP and CCK, which may be related to its upregulation of CB1R and downregulation of COX-2.



Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy

The present data indicates that several antimigraine agents exhibit marked 5-HT1A receptor activity and that although this is unlikely to be important for prophylactic action it may be relevant to the ancilliary properties of drugs used for acute migraine treatment.

Alniditan, a new 5-hydroxytryptamine1D agonist and migraine-abortive agent: ligand-binding properties of human 5-hydroxytryptamine1D alpha, human 5-hydroxytryptamine1D beta, and calf 5-hydroxytryptamine1D receptors investigated with [3H]5-hydroxytryptamine and [3H]alniditan.

It is demonstrated that alniditan is a potent agonist at 5-HT1D alpha and h5- HT1D beta receptors; its properties probably underlie its cranial vasoconstrictive and antimigraine properties.

5HT1F- and 5HT7-receptor agonists for the treatment of migraines.

  • R. Agosti
  • Biology, Psychology
    CNS & neurological disorders drug targets
  • 2007
The recent clone of 5-HT(1F) receptor together with data showing that sumatriptan exerts high affinity for this receptor subtype generated high expectations, suggesting a potential role for the migraine prophylaxis are discussed.

The Pharmacology of the Novel 5-HT1-Like Receptor Agonist, GR43175

Its vasoconstrictor action can be shown to be localized even further to arteriovenous anastomoses (shunts) within the carotid circulation, in such a way that blood flow to the brain as well as to extracerebral capillary beds remains unaffected or may even be increased.

Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan

Lasmiditan presents a unique pyridinoyl-piperidine scaffold not found in any other antimigraine class, whose chemical structure and pharmacological profile clearly distinguish it from the triptans.

Co-localization of 5-HT1B/1D/1F receptors and glutamate in trigeminal ganglia in rats

  • Q. Ma
  • Biology
  • 2001
The results suggest that 5-HT1B/1D/1F receptor agonists may modulate glutamate release, and that one mechanism of their anti-migraine action could be the blockade of glutamate release.

Operational characteristics of the 5-HT1-like receptors mediating external carotid vasoconstriction in vagosympathectomized dogs

The above findings suggest that the sumatriptan-sensitive 5-HT1-like receptors mediating canine external carotid vasoconstriction resemble 5-ht1D receptors, probably of the 5- HT1Dβ subtype on the basis of the resistance to blockade by ritanserin.

International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).

It is evident that in the last decade or so, a vast amount of new information has become available concerning the various 5-HT receptor types and their characteristics, and it is important to rationalise in concert all of the available data from studies involving both operational approaches of the classical pharmacological type and those from molecular and cellular biology.