CGRP receptor antagonists: An expanding drug class for acute migraine?

Expert Opinion on Investigational Drugs

Volumn 21, Issue 6, 2012, Pages 807-818

  Negro, Andrea ^a   Lionetto, Luana ^a   Simmaco, Maurizio ^b   Martelletti, Paolo ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Calcitonin gene related peptide; CGRP receptor; CGRP receptor antagonists; Gepants; Migraine

Indexed keywords

ACETYLSALICYLIC ACID; BI 44370 TA; BMS 927711; CALCITONIN GENE RELATED PEPTIDE RECEPTOR ANTAGONIST; CAPROLACTAM; CYCLIC AMP; IBUPROFEN; MK 3207; NONSTEROID ANTIINFLAMMATORY AGENT; OLCEGEPANT; PARACETAMOL; PLACEBO; RECEPTOR ACTIVITY MODIFYING PROTEIN 1; RIZATRIPTAN; SEROTONIN 1B AGONIST; SEROTONIN 1B RECEPTOR; TELCAGEPANT; TRIPTAN DERIVATIVE; UNCLASSIFIED DRUG; ZOLMITRIPTAN;

ACUTE DISEASE; ARTERY DILATATION; CARDIOVASCULAR DISEASE; CHEST TIGHTNESS; CLINICAL TRIAL (TOPIC); CLUSTER HEADACHE; DIZZINESS; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; HUMAN; MENINGEAL ARTERY; MIGRAINE; NAUSEA; PAIN; PHASE 2 CLINICAL TRIAL (TOPIC); PRIMARY HEADACHE; PROTEIN BINDING; PROTEIN BLOOD LEVEL; PUBLISHING; REVIEW; SOMNOLENCE; XEROSTOMIA;

ANIMALS; AZEPINES; DIPEPTIDES; DRUG DESIGN; HUMANS; IMIDAZOLES; MIGRAINE DISORDERS; QUINAZOLINES; RECEPTORS, CALCITONIN GENE-RELATED PEPTIDE; TRYPTAMINES;

EID: 84861073280     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2012.681044     Document Type: Review

References (106)

1. Stewart WF, Simon D, Shechter A, et al. Population variation in migraine prevalence: a meta-analysis. J Clin Epidemiol 1995;48(2):269-80
2. Graham J, Wolff H. Mechanism of migraine headache and action of ergotamine tartrate. Arch Neurol Psychiatry 1938;39:737-63
3. Parsons AA, Strijbos PJ. The neuronal versus vascular hypothesis of migraine and cortical spreading depression. Curr Opin Pharmacol 2003;3:73-7 (Pubitemid 36131330)
4. Buzzi MG, Bonamini M, Moskowitz MA. Neurogenic model of migraine. Cephalalgia 1995;15:277-80
5. Goadsby PJ, Charbit AR, Andreou AP, et al. Neurobiology of migraine. Neuroscience 2009;161:327-41
6. McCulloch J, Uddman R, Kingman TA, et al. Calcitonin gene-related peptide: functional role in cerebrovascular regulation. Proc Natl Acad Sci USA 1986;83:5731-5 (Pubitemid 16001291)
7. O'Connor TP, Van der Kooy D. Pattern of intracranial and extracranial projections of trigeminal ganglion cells. J Neurosci 1986;6:2200-7 (Pubitemid 16043662)
8. Edvinsson L. Calcitonin gene-related peptide (CGRP) and the pathophysiology of headache. CNS Drugs 2001;15:745-53 (Pubitemid 33065425)
9. Goadsby PJ, Edvinsson L, Ekman R. Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 1988;23:193-6 (Pubitemid 18081459)
10. Kurosawa M, Messlinger K, Pawlak M, et al. Increase of meningeal blood flow after electrical stimulation of rat dura mater encephali: mediation by calcitonin gene-related peptide. Br J Pharmacol 1995;114:1397-02
11. Edvinsson L, Mulder H, Goadsby PJ, et al. Calcitonin gene-related peptide and nitric oxide in the trigeminal ganglion: cerebral vasodilatation from trigeminal nerve stimulation involves mainly calcitonin generelated peptide. J Auton Nerv Syst 1998;70:15-22 (Pubitemid 28302583)
12. Kristiansen KA, Edvinsson L. Neurogenic inflammation: a study of rat trigeminal ganglion. J Headache Pain 2010;11:485-95
13. Edvinsson L. Blockade of CGRP receptors in the intracranial vasculature: a new target in the treatment of headache. Cephalalgia 2004;24:611-22 (Pubitemid 39061250)
14. Edvinsson L, Uddman R. Neurobiology in primary headaches. Brain Res Brain Res Rev 2005;48:438-56 (Pubitemid 40731510)
15. Jansen-Olesen I, Mortensen A, Edvinsson L. Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase. Cephalalgia 1996;16:310-16 (Pubitemid 26271251)
16. Edvinsson L, Ekman R, Jansen I, et al. Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects. J Cereb Blood Flow Metab 1987;7:720-8 (Pubitemid 18029813)
17. Lassen LH, Jacobsen VB, Haderslev PA, et al. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. J Headache Pain 2008;9:151-7
18. Gray DW, Marshall I. Nitric oxide synthesis inhibitors attenuate calcitonin gene-related peptide endothelium-dependent vasorelaxation in rat aorta. Eur J Pharacol 1992;212:37-42
19. Raddino R, Pela G, Manca C, et al. Mechanism of action of human calcitonin generelated peptide in rabbit heart and in human mammary arteries. J Cardiovasc Pharmacol 1997;29:463-70 (Pubitemid 27212749)
20. Li J, Vause CV, Durham PL. Calcitonin gene-related peptide stimulation of nitric oxide synthesis and release from trigeminal ganglion glial cells. Brain Res 2008;1196:22-32
21. Wei EP, Moskowitz MA, Boccalini P, et al. Calcitonin gene-related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles. Circ Res 1992;70:1313-19
22. Grant AD, Pinter E, Salmon AM, Brain SD. An examination of neurogenic mechanisms involved in mustard oil-induced inflammation in the mouse. Eur J Pharmacol 2005;507(1-3):273-80 (Pubitemid 40126864)
23. Wimalawansa SJ. Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr Rev 1996;17:533-85 (Pubitemid 26346642)
24. van Rossum D, Hanisch UK, Quirion R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev 1997(5):649-78 (Pubitemid 27458805)
25. Christopoulos G, Paxinos G, Huang XF, et al. Comparative distribution of receptors for amylin and the related peptides calcitonin gene related peptide and calcitonin in rat and monkey brain. Can J Physiol Pharmacol 1995;73:1037-41
26. Tsai SH, Tew JM, McLean JH, et al. Cerebral arterial innervation by nerve fibers containing calcitonin gene-related peptide (CGRP): I. Distribution and origin of CGRP perivascular innervation in the rat. J Comp Neurol 1988;271:435-44
27. Eftekhari S, Salvatore CA, Calamari A, et al. Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion. Neuroscience 2010;169:683-96
28. Uddman R, Edvinsson L, Ekman R, et al. Innervation of the feline cerebral vasculature by nerve fibers containing calcitonin gene-related peptide: trigeminal origin and co-existence with substance P. Neurosci Lett 1985;62:131-6 (Pubitemid 16205735)
29. Jansen I, Uddman R, Hocherman M, et al. Localization and effects of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide in human temporal arteries. Ann Neurol 1986;20:496-501 (Pubitemid 16005668)
30. Jansen I, Uddman R, Ekman R, et al. Distribution and effects of neuropeptide Y, vasoactive intestinal peptide, substance P, and calcitonin generelated peptide in human middle meningeal arteries: comparison with cerebral and temporal arteries. Peptides 1992;13:527-36
31. Gupta S, Amrutkar DV, Mataji A, et al. Evidence for CGRP re-uptake in rat dura mater encephali. Br J Pharmacol 2010;161:1885-98
32. Arulmani U, Maassenvandenbrink A, Villalon CM, et al. Calcitonin gene-related peptide and its role in migraine pathophysiology. Eur J Pharmacol 2004;500:315-30 (Pubitemid 39304018)
33. Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990;28:183-7 (Pubitemid 20244522)
34. Gallai V, Sarchielli P, Floridi A, et al. Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. Cephalalgia 1995;15:384-90
35. Juhasz G, Zsombok T, Modos EA, et al. NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release. Pain 2003;106:461-70 (Pubitemid 37505895)
36. Fanciullacci M, Alessandri M, Figini M, et al. Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack. Pain 1995;60:119-23
37. Cady RK, Vause CV, Ho TW, et al. Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan. Headache 2009;49:1258-66
38. Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993;33:48-56 (Pubitemid 23009909)
39. Goadsby PJ, Edvinsson L. Neuropeptide changes in a case of chronic paroxysmal hemicrania-evidence for trigemino-parasympathetic activation. Cephalalgia 1996;16:448-50 (Pubitemid 26338478)
40. Ashina M, Bendtsen L, Jensen R, et al. Plasma levels of calcitonin gene-related peptide in chronic tension-type headache. Neurology 2000;55:1335-40
41. Hansen JM, Hauge AW, Olesen J, et al. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia 2010;30:1179-86 .
42. Hansen JM, Thomsen LL, Olesen J, et al. Calcitonin gene-related peptide does not cause migraine attacks in patients with familial hemiplegic migraine. Headache 2011;51:544-53
43. Tvedskov JF, Lipka K, Ashina M, et al. No increase of calcitonin gene-related peptide in jugular blood during migraine. Ann Neurol 2005;58:561-8 (Pubitemid 41377219)
44. Goadsby PJ, Lipton RB, Ferrari MD. Migraine: current understanding and treatment. N Engl J Med 2002;346:257-70
45. Longmore J, Shaw D, Smith D, et al. Differential distribution of 5HT1D-and 5HT1B-immunoreactivity within the human trigeminocerebrovascular system: implications for the discovery of new antimigraine drugs. Cephalalgia 1997;17:833-42 .
46. Potrebic S, Ahn AH, Skinner K, et al. Peptidergic nociceptors of both trigeminal and dorsal root ganglia express serotonin1D receptors: implications for the selective antimigraine action of triptans. J Neurosci 2003;23:10988-97 (Pubitemid 37499709)
47. Ashgar MS, Hansen AE, Kapijimpanga T, et al. Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in healthy volunteers. Neurology 2010;75:1520-6
48. Villalon CM, Centurion D, Valdivia LF, et al. An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc 2002;45:199-210
49. Williamson DJ, Hargreaves RJ. Neurogenic inflammation in the context of migraine. Microsc Res Tech 2001;53:167-8
50. Summ O, Andreou AP, Akerman S, et al. A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches. J Headache Pain 2010;11:477-83
51. Geraud G, Keywood C, Senard JM. Migraine headache recurrence: relationship to clinical, pharmacological, and pharmacokinetic properties of triptans. Headache 2003;43:376-88 . (Pubitemid 36417768)
52. Diener HC, Katsarava Z. Medication overuse headache. Curr Med Res Opin 2001;17:S17-21
53. Negro A, Martelletti P. Chronic migraine plus medication overuse headache: two entities or not? J Headache Pain 2011;12:593-60
54. Meng ID, Dodick D, Ossipov MH, et al. Pathophysiology of medication overuse headache: insights and hypotheses from preclinical studies. Cephalalgia 2011;31:851-60
55. Visser WH, Jaspers NM, de Vriend RH, et al. Chest symptoms after sumatriptan: a two-year clinical practice review in 735 consecutive migraine patients. Cephalalgia 1996;16:554-9 (Pubitemid 27015929)
56. Dodick D, Lipton RB, Martin V, et al. Consensus statement: cardiovascular safety profile of triptans (5-HT1B/1D agonists) in the acute treatment of migraine. Headache 2004;44:414-25 . (Pubitemid 38685549)
57. Goadsby PJ. Post-triptan era for the treatment of acute migraine. Curr Pain Headache Rep 2004;8:393-8 (Pubitemid 39345309)
58. Durham PL. CGRP receptor antagonist: a new choice for acute treatment of migraine? Curr Opin Investig Drugs 2004;5:731-5
59. Geppetti P, Capone JG, Trevisani M, et al. CGRP and migraine: neurogenic inflammation revisited. J Headache Pain 2005;6:61-70 (Pubitemid 40667556)
60. Goadsby PJ. Calcitonin gene-related peptide antagonists as treatments of migraine and other primary headaches. Drugs 2005;65:2557-67 (Pubitemid 43049952)
61. Iovino M, Feifel U, Yong CL, et al. Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective small molecule calcitonin gene-related peptide receptor antagonist, following single intravenous administration in healthy volunteers. Cephalalgia 2004;24:645-56 (Pubitemid 39061254)
62. Williams TM, Stump CA, Nguyen DN, et al. Non-peptide calcitonin gene-related peptide receptor antagonists from a benzodiazepinone lead. Bioorg Med Chem Lett 2006;16:2595-8
63. Bell IM, Bednar RA, Fay JF, et al. Identification of novel, orally bioavailable spirohydantoin CGRP receptor antagonists. Bioorg Med Chem Lett 2006;16:6165-9 (Pubitemid 44709924)
64. Burgey CS, Stump CA, Nguyen DN, et al. Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: optimization of the 4-substituted piperidine. Bioorg Med Chem Lett 2006;16:5052-6 (Pubitemid 44247711)
65. Shaw AW, Paone DV, Nguyen DN, et al. Caprolactams as potent CGRP receptor antagonists for the treatment of migraine. Bioorg Med Chem Lett 2007;17:4795-8 (Pubitemid 47187710)
66. ter Haar E, Koth CM, Abdul-Manan N, et al. Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism. Structure 2010;18:1083-93
67. Paone DV, Shaw AW, Nguyen DN, et al. Potent, orally bioavailable calcitonin gene-related peptide receptor antagonists for the treatment of migraine: discovery of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2- trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl) piperidine-1-carboxamide (MK-0974). J Med Chem 2007;50:5564-7 (Pubitemid 350106011)
68. Bell IM, Gallicchio SN, Wood MR, et al. Discovery of MK-3207: a highly potent, orally bioavailable CGRP receptor antagonist. ACS Med Chem Lett 2010;1:24-9
69. Paone DV, Nguyen DN, Shaw AW, et al. Orally bioavailable imidazoazepanes as calcitonin gene-related peptide (CGRP) receptor antagonists: discovery of MK-2918. Bioorg Med Chem Lett 2011;21:2683-6
70. Fraser NJ, Wise A, Brown J, et al. The amino terminus of receptor activity modifying proteins is a critical determinant of glycosylation state and ligand binding of calcitonin receptor-like receptor. Mol Pharmacol 1999;55:1054-9 (Pubitemid 29252372)
71. Hilairet S, Belanger C, Bertrand J, et al. Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin. J Biol Chem 2001;276:42182-90
72. Kamitani S, Sakata T. Glycosylation of human CRLR at Asn123 is required for ligand binding and signaling. Biochim Biophys Acta 2001;1539:131-9 (Pubitemid 32522875)
73. Kuwasako K, Kitamura K, Nagoshi Y, et al. Identification of the human receptor activity-modifying protein 1 domains responsible for agonist binding specificity. J Biol Chem 2003;278:22623-30 (Pubitemid 36830320)
74. Ittner LM, Koller D, Muff R, et al. The N-terminal extracellular domain 23-60 of the calcitonin receptor-like receptor in chimeras with the parathyroid hormone receptor mediates association with receptor activity-modifying protein 1. Biochemistry 2005;44:5749-54 (Pubitemid 40525111)
75. Koller D, Born W, Leuthauser K, et al. The extreme N-terminus of the calcitonin-like receptor contributes to the selective interaction with adrenomedullin or calcitonin gene-related peptide. FEBS Lett 2002;531:464-8 (Pubitemid 35336070)
76. Hay DL, Christopoulos G, Christopoulos A, et al. Determinants of 1-piperidinecarboxamide, N-[2-[[5-amino-l-[[4-(4-pyridinyl)-lpiperazinyl] carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1, 4-dihydro-2-oxo-3(2 H)-quinazolinyl) (BIBN4096BS) affinity for calcitonin gene-related peptide and amylin receptors-the role of receptor activity modifying protein 1. Mol Pharmacol 2006;70:1984-91 (Pubitemid 44771914)
77. Mallee JJ, Salvatore CA, LeBourdelles B, et al. Receptor activity-modifying protein 1 determines the species selectivity of non-peptide CGRP receptor antagonists. J Biol Chem 2002;277:14294-8 (Pubitemid 34968045)
78. Salvatore CA, Mallee JJ, Bell IM, et al. Identification and pharmacological characterization of domains involved in binding of CGRP receptor antagonists to the calcitonin-like receptor. Biochemistry 2006;45:1881-7 (Pubitemid 43222131)
79. Salvatore CA, Hershey JC, Corcoran HA, et al. Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2- trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b] pyridin-1-yl)piperidine-1-carboxamide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine. J Pharmacol Exp Ther 2008;324:416-21 (Pubitemid 351185864)
80. Salvatore CA, Moore EL, Calamari A, et al. Pharmacological properties of MK-3207, a potent and orally active calcitonin gene-related peptide receptor antagonist. Pharmacol Exp Ther 2010;333:152-60
81. Troltzsch M, Denekas T, Messlinger K. The calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS reduces neurogenic increases in dural blood flow. Eur J Pharmacol 2007;562:103-10 (Pubitemid 46466759)
82. Kapoor K, Arulmani U, Heiligers JP, et al. Effects of the CGRP receptor antagonist BIBN4096BS on capsaicin-induced carotid haemodynamic changes in anaesthetised pigs. Br J Pharmacol 2003;140:329-38 (Pubitemid 37249193)
83. Kapoor K, Arulmani U, Heiligers JP, et al. Effects of BIBN4096BS on cardiac output distribution and on CGRP-induced carotid haemodynamic responses in the pig. Eur J Pharmacol 2003;475:69-77 (Pubitemid 37088008)
84. Moreno MJ, Abounader R, Hebert E, et al. Efficacy of the non-peptide CGRP receptor antagonist BIBN4096BS in blocking CGRP-induced dilations in human and bovine cerebral arteries: potential implications in acute migraine treatment. Neuropharmacology 2002;42:568-76 (Pubitemid 34304249)
85. Arulmani U, Schuijt MP, Heiligers JP, et al. Effects of the CGRP receptor antagonist BIBN4096BS on CGRP-induced regional haemodynamic changes in anaesthetised rats. Basic Clin Pharmacol Toxicol 2004;94:291-7 (Pubitemid 38954896)
86. Wu DM, van Zwieten PA, Doods HN. Effects of calcitonin gene-related peptide and BIBN4096BS on myocardial ischemia in anesthetized rats. Acta Pharmacol Sin 2001;22:588-94 (Pubitemid 32656485)
87. Petersen KA, Birk S, Doods H, et al. Inhibitory effect of BIBN4096BS on cephalic vasodilatation induced by CGRP or transcranial electrical stimulation in the rat. Br J Pharmacol 2004;143:697-704 (Pubitemid 39611605)
88. Petersen KA, Birk S, Lassen LH, et al. The CGRP-antagonist, BIBN4096BS does not affect cerebral or systemic haemodynamics in healthy volunteers. Cephalalgia 2005;25:139-47 (Pubitemid 40193957)
89. Fischer MJ, Koulchitsky S, Messlinger K. The nonpeptide calcitonin gene-related peptide receptor antagonist BIBN4096BS lowers the activity of neurons with meningeal input in the rat spinal trigeminal nucleus. J Neurosci 2005;25:5877-83 (Pubitemid 40911418)
90. Olesen J, Diener HC, Husstedt IW, et al. BIBN 4096 BS Clinical Proof of Concept Study Group. BIBN 4096 BS Clinical Proof of Concept Study Group. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 2004;350:1104-10
91. Farinelli I, De Filippis S, Coloprisco G, et al. Future drugs for migraine. Intern Emerg Med 2009;4(5):367-73
92. Ho TW, Mannix LK, Fan X, et al. MK-0974 Protocol 004 study group. Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology 2008;70:1304-12 (Pubitemid 351550355)
93. Hewitt DJ, Martin V, Lipton RB, et al. Randomized controlled study of telcagepant plus Ibuprofen or acetaminophen in migraine. Headache 2011;51:533-43
94. Ho AP, Dahlof CG, Silberstein SD, et al. Randomized, controlled trial of telcagepant over four migraine attacks. Cephalalgia 2010;30:1443-57
95. Connor KM, Aurora SK, Loeys T, et al. Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial. Headache 2011;51:73-84
96. Ho TW, Ferrari MD, Dodick DW, et al. 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 2008;372:2115-23 .
97. Connor KM, Shapiro RE, Diener HC, et al. Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology 2009;73:970-7
98. Ho TW, Ho AP, Chaitman BR, et al. Randomized, controlled study of telcagepant in patients with migraine and Coronary Artery disease. Headache 2012;published online Jan 6 2012; doi: 10.1111/j.1526-4610.2011.02052.x
99. van der Schueren BJ, Blanchard R, Murphy MG, et al. The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men. Br J Clin Pharmacol 2011;71:708-17
100. Available from: http://www.merck.com/newsroom/news-release-archive/ financial/2011-0729.html
101. Hewitt DJ, Aurora SK, Dodick DW, et al. Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia 2011;31:712-22
102. Diener HC, Barbanti P, Dahlof C, et al. BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study. Cephalalgia 2011;31:573-84
103. Ferrari MD, Roon KI, Lipton RB, et al. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001;358:1668-75 . (Pubitemid 33124324)
104. Tfelt-Hansen P. Excellent tolerability but relatively low initial clinical efficacy of telcagepant in migraine. Headache 2011;51(1):118-23
105. Tfelt-Hansen P. Optimal balance of efficacy and tolerability of oral triptans and telcagepant: a review and a clinical comment. J Headache Pain 2011;12:275-80
106. Tfelt-Hansen P, Olesen J. Possible site of action of CGRP antagonists in migraine. Cephalalgia 2011;31(6):748-50