Telcagepant: Difference between revisions

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| smiles = Fc1c(F)cccc1C(CN(C3=O)CC(F)(F)F)CCC3NC(=O)N5CCC(CC5)n2c4cccnc4nc2=O
| smiles = Fc1c(F)cccc1C(CN(C3=O)CC(F)(F)F)CCC3NC(=O)N5CCC(CC5)n2c4cccnc4nc2=O
}}
}}

'''Telcagepant''' (formerly '''MK-0974''') was an investigational drug for the acute treatment and prevention of [[migraine]], developed by [[Merck & Co.]] In the acute treatment of migraine, it was found to have equal potency to [[rizatriptan]]<ref>{{cite journal|date=Apr 2008|journal=Neurology|volume=70|issue=16|pages=1304–12|doi=10.1212/01.WNL.0000286940.29755.61|author=Ho, Tw; Mannix, Lk; Fan, X; Assaid, C; Furtek, C; Jones, Cj; Lines, Cr; Rapoport, Am; Mk-0974, Protocol, 004, Study, Group|title=Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine|pmid=17914062}}</ref> and [[zolmitriptan]]<ref>{{cite journal |author=Ho TW, Ferrari MD, Dodick DW, ''et al.'' |title=Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial |journal=Lancet |volume=372 |issue=9656 |pages=2115–23 |date=December 2008 |pmid=19036425 |doi=10.1016/S0140-6736(08)61626-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61626-8}}</ref> in two Phase III [[clinical trial]]s. The company has now terminated development of the drug.
'''Telcagepant''' ([[International Nonproprietary Name|INN]]) (code name '''MK-0974''') 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.]] In the acute treatment of migraine, it was found to have equal potency to [[rizatriptan]]<ref>{{cite journal|date=Apr 2008|journal=Neurology|volume=70|issue=16|pages=1304–12|doi=10.1212/01.WNL.0000286940.29755.61|author=Ho, Tw; Mannix, Lk; Fan, X; Assaid, C; Furtek, C; Jones, Cj; Lines, Cr; Rapoport, Am; Mk-0974, Protocol, 004, Study, Group|title=Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine|pmid=17914062}}</ref> and [[zolmitriptan]]<ref>{{cite journal |author=Ho TW, Ferrari MD, Dodick DW, ''et al.'' |title=Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial |journal=Lancet |volume=372 |issue=9656 |pages=2115–23 |date=December 2008 |pmid=19036425 |doi=10.1016/S0140-6736(08)61626-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61626-8}}</ref> in two Phase III [[clinical trial]]s. The company has now terminated development of the drug.


==Mechanism of action==
==Mechanism of action==

Revision as of 20:14, 1 January 2015

Telcagepant
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • Experimental
Pharmacokinetic data
Elimination half-life5-8 hours
Identifiers
  • N-[(3R,6S)-6-(2,3-Difluorophenyl)hexahydro-2-oxo-1-(2,2,2-trifluoroethyl)-1H-azepin-3-yl]-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-1-yl)-1-piperidinecarboxamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC26H27F5N6O3
Molar mass566.5283 g·mol−1
3D model (JSmol)
  • Fc1c(F)cccc1C(CN(C3=O)CC(F)(F)F)CCC3NC(=O)N5CCC(CC5)n2c4cccnc4nc2=O

  • O=C(N[C@H]2C(=O)N(CC(F)(F)F)C[C@H](c1cccc(F)c1F)CC2)N5CCC(N4c3cccnc3NC4=O)CC5
  • InChI=1S/C26H27F5N6O3/c27-18-4-1-3-17(21(18)28)15-6-7-19(23(38)36(13-15)14-26(29,30)31)33-24(39)35-11-8-16(9-12-35)37-20-5-2-10-32-22(20)34-25(37)40/h1-5,10,15-16,19H,6-9,11-14H2,(H,33,39)(H,32,34,40)/t15-,19-/m1/s1 checkY
  • Key:CGDZXLJGHVKVIE-DNVCBOLYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Telcagepant (INN) (code name MK-0974) 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. In the acute treatment of migraine, it was found to have equal potency to rizatriptan[1] and zolmitriptan[2] in two Phase III clinical trials. The company has now terminated development of the drug.

Mechanism of action

The calcitonin gene-related peptide (CGRP) is a strong vasodilator primarily found in nervous tissue. Since vasodilation in the brain is thought to be involved in the development of migraine and CGRP levels are increased during migraine attacks, this peptide may be an important target for potential new antimigraine drugs.

Telcagepant acts as a calcitonin gene-related peptide receptor (CRLR) antagonist and blocks this peptide. It is believed to constrict dilated blood vessels within the brain.[3]

Termination of a clinical trial

A Phase IIa clinical trial studying telcagepant for the prophylaxis of episodic migraine was stopped on March 26, 2009 after the "identification of two patients with significant elevations in serum transaminases".[4] A memo to study locations stated that telcagepant had preliminarily been reported to increase the hepatic liver enzyme alanine transaminase (AST) levels in "11 out of 660 randomized (double-blinded) study participants." All study participants were told to stop taking the medication.[5]

On July 29, 2011, it was reported that Merck & Co. were discontinuing the clinical development program for telcagepant. According to Merck, "[t]he decision is based on an assessment of data across the clinical program, including findings from a recently completed six-month Phase III study".[6]

See also

References

  1. ^ Ho, Tw; Mannix, Lk; Fan, X; Assaid, C; Furtek, C; Jones, Cj; Lines, Cr; Rapoport, Am; Mk-0974, Protocol, 004, Study, Group (Apr 2008). "Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine". Neurology. 70 (16): 1304–12. doi:10.1212/01.WNL.0000286940.29755.61. PMID 17914062.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  2. ^ Ho TW, Ferrari MD, Dodick DW; et al. (December 2008). "Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial". Lancet. 372 (9656): 2115–23. doi:10.1016/S0140-6736(08)61626-8. PMID 19036425. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  3. ^ Molecule of the Month February 2009
  4. ^ Clinical trial number NCT00797667 for "MK0974 for Migraine Prophylaxis in Patients With Episodic Migraine" at ClinicalTrials.gov
  5. ^ Merck & Co.: Memo to all US study locations involved in protocol MK0974-049
  6. ^ Merck Announces Second Quarter 2011 Financial Results


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