Ubrogepant

Last updated

Ubrogepant
Ubrogepant.svg
Clinical data
Trade names Ubrelvy
Other namesMK-1602
AHFS/Drugs.com Monograph
MedlinePlus a620016
License data
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 87% (in vitro)
Elimination half-life 5-7 hrs
Excretion fecal/biliary
Identifiers
  • (6S)-N-[(3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-3-piperidinyl]-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide
CAS Number
PubChem CID
PubChemSID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C29H26F3N5O3
Molar mass 549.554 g·mol−1
3D model (JSmol)
  • C[C@@H]1[C@H](c2ccccc2)C[C@H](NC(=O)c2cnc3c(c2)C[C@@]2(C3)C(=O)Nc3ncccc32)C(=O)N1CC(F)(F)F
  • InChI=1S/C29H26F3N5O3/c1-16-20(17-6-3-2-4-7-17)11-22(26(39)37(16)15-29(30,31)32)35-25(38)19-10-18-12-28(13-23(18)34-14-19)21-8-5-9-33-24(21)36-27(28)40/h2-10,14,16,20,22H,11-13,15H2,1H3,(H,35,38)(H,33,36,40)/t16-,20-,22+,28+/m1/s1
  • Key:DDOOFTLHJSMHLN-ZQHRPCGSSA-N

Ubrogepant, sold under the brand name Ubrelvy, is a medication used for the acute (immediate) treatment of migraine with or without aura (a sensory phenomenon or visual disturbance) in adults. [3] [4] It is not indicated for the preventive treatment of migraine. [5] Ubrogepant is a small-molecule calcitonin gene-related peptide receptor antagonist. [6] [7] It is the first drug in this class approved for the acute treatment of migraine. [8]

Contents

The most common side effects are nausea, tiredness and dry mouth. [5] Ubrogepant is contraindicated for co-administration with strong CYP3A4 inhibitors. [5]

History

Ubrogepant, also known as MK-1602, was discovered by scientists at Merck. [9]

The effectiveness of ubrogepant for the acute treatment of migraine was demonstrated in two randomized, double-blind, placebo-controlled trials. [5] In these studies, 1,439 adult patients with a history of migraine, with and without aura, received the approved doses of ubrogepant to treat an ongoing migraine. [5] In both studies, the percentages of patients achieving pain relief two hours after treatment (defined as a reduction in headache severity from moderate or severe pain to no pain) and whose most bothersome migraine symptom (nausea, light sensitivity or sound sensitivity) stopped two hours after treatment were significantly greater among patients receiving ubrogepant (19–21% depending on the dose) compared to those receiving placebo (12%). [5] [10] Patients were allowed to take their usual acute treatment of migraine at least two hours after taking ubrogepant. [5] 23% of patients were taking a preventive medication for migraine. [5]

In December 2019, the U.S. Food and Drug Administration approved Ubrelvy produced by Allergan USA, Inc. for treatment of migraine after onset. [5] [11]

Related Research Articles

<span class="mw-page-title-main">Migraine</span> Disorder resulting in recurrent moderate-severe headaches

Migraine is a genetically influenced complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea and light and sound sensitivity. Other characterizing symptoms may include nausea, vomiting, cognitive dysfunction, allodynia, and dizziness. Exacerbation of headache symptoms during physical activity is another distinguishing feature. Up to one-third of migraine sufferers experience aura: a premonitory period of sensory disturbance widely accepted to be caused by cortical spreading depression at the onset of a migraine attack. Although primarily considered to be a headache disorder, migraine is highly heterogenous in its clinical presentation and is better thought of as a spectrum disease rather than a distinct clinical entity. Disease burden can range from episodic discrete attacks, consisting of as little as several lifetime attacks, to chronic disease.

<span class="mw-page-title-main">Sumatriptan</span> 5-HT receptor agonist medication used for migraines & cluster headaches

Sumatriptan, sold commonly under brand names Imitrex and Treximet among others, is a medication used to treat migraine headaches and cluster headaches. It is taken orally, intranasally, or by subcutaneous injection. Therapeutic effects generally occur within three hours.

<span class="mw-page-title-main">Triptan</span> Class of pharmaceutical drugs

Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, they do not provide preventive treatment and are not considered a cure. They are not effective for the treatment of tension–type headache, except in persons who also experience migraines. Triptans do not relieve other kinds of pain.

<span class="mw-page-title-main">Ziconotide</span> Drug for chronic pain

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Neurogenic inflammation is inflammation arising from the local release by afferent neurons of inflammatory mediators such as Substance P, Calcitonin Gene-Related Peptide (CGRP), neurokinin A (NKA), and endothelin-3 (ET-3). In such neurons, release of these pro-inflammatory mediators is thought to be triggered by the activation of ion channels that are the principal detectors of noxious environmental stimuli. In particular, the heat/capsaicin receptor TRPV1 and the irritant/wasabi receptor TRPA1. TRPA1 channels stimulated by lipopolysaccharide (LPS) may also cause acute neurogenic inflammation. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and calcitonin gene-related peptide; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established.

<span class="mw-page-title-main">Calcitonin gene-related peptide</span> Peptide hormone in animals

Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 (intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produced by thyroid C cells whilst CGRP is secreted and stored in the nervous system. This peptide, in humans, exists in two forms: CGRP alpha, and CGRP beta. α-CGRP is a 37-amino acid neuropeptide and is formed by alternative splicing of the calcitonin/CGRP gene located on chromosome 11. β-CGRP is less studied. In humans, β-CGRP differs from α-CGRP by three amino acids and is encoded in a separate, nearby gene. The CGRP family includes calcitonin (CT), adrenomedullin (AM), and amylin (AMY).

<span class="mw-page-title-main">Antimigraine drug</span> Medication intended to reduce the effects or intensity of migraine headache

Antimigraine drugs are medications intended to reduce the effects or intensity of migraine headache. They include drugs for the treatment of acute migraine symptoms as well as drugs for the prevention of migraine attacks.

<span class="mw-page-title-main">Liraglutide</span> Anti-diabetic medication

Liraglutide, sold under the brand names Victoza and Saxenda among others, is an anti-diabetic medication used to treat type 2 diabetes, and chronic obesity. It is a second-line therapy for diabetes following first-line therapy with metformin. Its effects on long-term health outcomes like heart disease and life expectancy are unclear. It is given by injection under the skin.

<span class="mw-page-title-main">Telcagepant</span> Chemical compound

Telcagepant (INN) is a calcitonin gene-related peptide receptor antagonist which was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co.

Preventive treatment of migraine can be an important component of migraine management. Such treatments can take many forms, including everything from surgery, taking certain drugs or nutritional supplements, to lifestyle alterations such as increased exercise and avoidance of migraine triggers.

<span class="mw-page-title-main">Lasmiditan</span> Chemical compound

Lasmiditan, sold under the brand name Reyvow, is a medication used for the acute treatment of migraine with or without aura in adults. It is not useful for prevention. It is taken by mouth.

Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. It is applied three times daily for a maximum of three months. Zucapsaicin is a member of phenols and a member of methoxybenzenes. It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1 that reduces pain, and improves articular functions. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use.

Calcitonin gene-related peptide (CGRP) receptor antagonists are a class of drugs that act as antagonists of the calcitonin gene-related peptide receptor (CGRPR).

Eptinezumab, sold under the brand name Vyepti, is a medication used for the preventive treatment of migraine in adults. It is a monoclonal antibody that targets calcitonin gene-related peptides (CGRP) alpha and beta. It is administered by intravenous infusion.

<span class="mw-page-title-main">Galcanezumab</span> Monoclonal antibody

Galcanezumab, sold under the brand name Emgality, is a humanized monoclonal antibody used for the prevention of migraine. It is also used for cluster headaches.

<span class="mw-page-title-main">Erenumab</span> Chemical compound

Erenumab, sold under the brand name Aimovig, is a medication which targets the calcitonin gene-related peptide receptor (CGRPR) for the prevention of migraine. It is administered by subcutaneous injection.

<span class="mw-page-title-main">Rimegepant</span> Medication for acute migraine in adults

Rimegepant, sold under the brand name Nurtec ODT among others, is a medication used for the acute treatment of migraine with or without aura in adults and the prophylactic/ preventive treatment of episodic migraine in adults. It is taken by mouth to dissolve on or under the tongue. It works by blocking CGRP receptors.

Fremanezumab, sold under the brand name Ajovy, is a medication used to prevent migraines in adults. It is given by injection under the skin.

<span class="mw-page-title-main">Atogepant</span> Chemical compound

Atogepant, sold under the brand name Qulipta among others, is a medication used to prevent migraines. It is a gepant, an orally active calcitonin gene-related peptide receptor antagonist.

<span class="mw-page-title-main">Zavegepant</span> Medication for treatment of migraine

Zavegepant, sold under the brand name Zavzpret, is a medication used for the treatment of migraine. Zavegepant is a calcitonin gene-related peptide receptor antagonist. It is sprayed into the nose. It is sold by Pfizer.

References

  1. "Ubrelvy Product information". Health Canada. Retrieved 2 January 2023.
  2. "Summary Basis of Decision - Ubrelvy". Health Canada . 30 March 2023. Retrieved 24 April 2023.
  3. 1 2 "Ubrelvy- ubrogepant tablet". DailyMed. Retrieved 4 June 2021.
  4. "Ubrogepant Prescribing Information" (PDF). FDA.gov. U.S. Food and Drug Administration. 2019.
  5. 1 2 3 4 5 6 7 8 9 "FDA approves new treatment for adults with migraine". U.S. Food and Drug Administration (FDA) (Press release). 23 December 2019. Archived from the original on 23 December 2019. Retrieved 23 December 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  6. Tfelt-Hansen P, Olesen J (April 2011). "Possible site of action of CGRP antagonists in migraine". Cephalalgia. 31 (6): 748–750. doi: 10.1177/0333102411398403 . PMID   21383046. S2CID   22049557.
  7. Spreitzer H (22 May 2018). "Neue Wirkstoffe: Ubrogepant". Österreichische Apotheker-Zeitung (in German) (11/2018).
  8. "What You Need to Know About Ubrelvy, First Acute CGRP Med Approved". Migraine Again. 28 January 2020. Retrieved 3 June 2021.
  9. Moore E, Fraley ME, Bell IM, Burgey CS, White RB, Li CC, et al. (January 2020). "Characterization of Ubrogepant: A Potent and Selective Antagonist of the Human Calcitonin Gene‒Related Peptide Receptor". The Journal of Pharmacology and Experimental Therapeutics: jpet.119.261065. doi: 10.1124/jpet.119.261065 . PMID   31992609. S2CID   210946813.
  10. Dodick DW, Lipton RB, Ailani J, Lu K, Finnegan M, Trugman JM, Szegedi A (December 2019). "Ubrogepant for the Treatment of Migraine". The New England Journal of Medicine. 381 (23): 2230–2241. doi: 10.1056/NEJMoa1813049 . PMID   31800988. S2CID   208645302.
  11. Maddipatla M (23 December 2019). "Allergan's acute migraine treatment wins U.S. FDA approval". Reuters. Retrieved 24 December 2019.