Drugs

, Volume 60, Issue 6, pp 1259–1287 | Cite as

Triptans in Migraine

A Comparative Review of Pharmacology, Pharmacokinetics and Efficacy
  • Peer Tfelt-Hansen
  • Peter De Vries
  • Pramod R. Saxena
Review Article

Abstract

Triptans are a new class of compounds developed for the treatment of migraine attacks. The first of the class, sumatriptan, and the newer triptans (zolmitriptan, naratriptan, rizatriptan, eletriptan, almotriptan and frovatriptan) display high agonist activity at mainly the serotonin 5-HT1b and 5-HT1d receptor subtypes. As expected for a class of compounds developed for affinity at a specific receptor, there are minor pharmacodynamic differences between the triptans.

Sumatriptan has a low oral bioavailability (14%) and all the newer triptans have an improved oral bioavailability and for one, risatriptan, the rate of absorption is faster. The half-lives of naratriptan, eletriptan and, in particular, frovatriptan (26 to 30h) are longer than that of sumatriptan (2h). These pharmacokinetic improvements of the newer triptans so far seem to have only resulted in minor differences in their efficacy in migraine.

Double-blind, randomised clinical trials (RCTs) comparing the different triptans and triptans with other medication should ideally be the basis for judging their place in migraine therapy. In only 15 of the 83 reported RCTs were 2 triptans compared, and in 11 trials triptans were compared with other drugs. Therefore, in all placebo-controlled randomised clinical trials, the relative efficacy of the triptans was also judged by calculating the therapeutic gain (i.e. percentage response for active minus percentage response for placebo). The mean therapeutic gain with subcutaneous sumatriptan 6mg (51%) was more than that for all other dosage forms of triptans (oral sumatriptan 100mg 32%; oral sumatriptan 50mg 29%; intranasal sumatriptan 20mg 30%; rectal sumatriptan 25mg 31%; oral zolmitriptan 2.5mg 32%; oral rizatriptan 10mg 37%; oral eletriptan 40mg 37%; oral almotriptan 12.5mg 26%). Compared with oral sumatriptan 100mg (32%), the mean therapeutic gain was higher with oral eletriptan 80mg (42%) but lower with oral naratriptan 2.5mg (22%) or oral frovatriptan 2.5mg (16%). The few direct comparative randomised clinical trials with oral triptans reveal the same picture. Recurrence of headache within 24 hours after an initial successful response occurs in 30 to 40% of sumatriptan-treated patients. Apart from naratriptan, which has a tendency towards less recurrence, there appears to be no consistent difference in recurrence rates between the newer triptans and sumatriptan. Rizatriptan with its shorter time to maximum concentration (tmax) tended to produce a quicker onset of headache relief than sumatriptan and zolmitriptan.

The place of triptans compared with non-triptan drugs in migraine therapy remains to be established and further RCTs are required.

References

  1. 1.
    Saxena PR, De Vries P, Villalón CM. 5-HT1-like receptors: a time to bid goodbye. Trends Pharmacol Sci 1998; 19: 311–6PubMedCrossRefGoogle Scholar
  2. 2.
    De Vries P, Villalón CM, Saxena PR. Pharmacology of triptans. Emerg Drugs 1999; 4: 107–25CrossRefGoogle Scholar
  3. 3.
    Humphrey PPA, Feniuk W. Mode of action of the anti-migraine drug sumatriptan. Trends Pharmacol Sci 1991; 12: 444–6PubMedCrossRefGoogle Scholar
  4. 4.
    Tfelt-Hansen P. Sumatriptan for the treatment of migraine attacks — a review of controlled clinical trials. Cephalalgia 1993; 13: 238–44PubMedCrossRefGoogle Scholar
  5. 5.
    Plosker GL, McTavish D. Sumatriptan. A reappraisal of its pharmacology and therapeutic efficacy in the acute treatment of migraine and cluster headache. Drugs 1994; 47: 622–51Google Scholar
  6. 6.
    Pilgrim AJ. Methodology of clinical trials of sumatriptan in migraine and cluster headache. Eur Neurol 1991; 31: 295–9PubMedCrossRefGoogle Scholar
  7. 7.
    Wilkinson M, Pfaffenrath V, Schoenen J, et al. Migraine and cluster headache — their management with sumatriptan: a critical review of the current clinical experience. Cephalalgia 1995; 15: 337–57PubMedGoogle Scholar
  8. 8.
    Dechant KL, Clissold SP. Sumatriptan. A review of its pharma-codynamic and phannacokinetic properties, and therapeutic efficacy in the acute treatment of migraine and cluster headache. Drugs 1992; 43: 776–98Google Scholar
  9. 9.
    Perry CN, Markham A. Sumatriptan. An updated review of its use in migraine. Drugs 1998; 55: 889–922Google Scholar
  10. 10.
    Ryan Jr RE, Elkind A, Goldstein J. Twenty-four-hour effectiveness of BMS 180048 in the acute treatment of migraine headaches. Headache 1997; 37: 245–8PubMedCrossRefGoogle Scholar
  11. 11.
    Couch JRJ, Saper J, Meloche JP. Treatment of migraine with BMS 180048: response at 2 hours. North American BMS 180048 Study Group. Headache 1996; 36: 523–30Google Scholar
  12. 12.
    Yocca FD, Gylys JA, Smith DW, et al. BMS-181885: a clinically effective migraine abortive with peripherovascular and neuronal 5-HT1d agonist properties. Cephalalgia 1997; 17: 404Google Scholar
  13. 13.
    Goldstein J, Dahlöf CG, Diener H-C, et al. Alniditan in the acute treatment of migraine attacks: a subcutaneous dose-finding study. Cephalalgia 1996; 16: 497–502PubMedCrossRefGoogle Scholar
  14. 14.
    Leysen JE, Gommeren W, Heylen L, et al. Alniditan, a new 5-hydroxytryptamine1D agonist and migraine-abortive agent: ligand-binding properties of human 5-hydroxytryptamine1Dα, human 5-hydroxytryptamine1Dβ, and calf 5-hydroxytryptamine1D receptors investigated with [3H]5-hydroxytryptamine and [3H]alniditan. Mol Pharmacol 1996; 50: 1567–80PubMedGoogle Scholar
  15. 15.
    Newman-Tancredi A, Conte C, Chaput C, et al. Agonist activity of antimigraine drugs at recombinant human 5-HT1a receptors: potential implications for prophylactic and acute therapy. Naunyn Schmiedebergs Arch Pharmacol 1997; 355: 682–8PubMedCrossRefGoogle Scholar
  16. 16.
    Martin GR, Robertson AD, MacLennan SJ, et al. Receptor specificity and trigemino-vascular inhibitory actions of a novel 5-HT1b/1d receptor partial agonist, 311C90 (zolmitriptan)®. BrJ Pharmacol 1997; 121: 157–64CrossRefGoogle Scholar
  17. 17.
    Connor HE, Feniuk W, Beattie DT, et al. Naratriptan: biological profile in animal models relevant to migraine. Cephalalgia 1997; 1997: 145–52CrossRefGoogle Scholar
  18. 18.
    Napier C, Stewart M, Melrose H, et al. Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1b and 5-HT1d receptors. Eur J Pharmacol 1999; 368: 259–68PubMedCrossRefGoogle Scholar
  19. 19.
    Bou J, Domenech T, Gras J, et al. Pharmacological profile of almotriptan, a novel antimigraine agent. Cephalalgia 1997; 17: 421Google Scholar
  20. 20.
    Brown A, Parsons AA, Raval P, et al. SB 209509 (VML 251), a potent constrictor of rabbit basilar artery with high affinity and selectivity for human 5-HT1d receptors. Br J Pharmacol 1996; 119: 110PGoogle Scholar
  21. 21.
    Wurch T, Palmier C, Colpaert FC, et al. Recombinant saphenous vein 5-HT1b receptors of the rabbit: comparative pharmacology with human 5-HT1b receptors. Br J Pharmacol 1997; 120: 153–9PubMedCrossRefGoogle Scholar
  22. 22.
    Wainscott DB, Johnson KW, Phebus LA, et al. Human 5-HT1F receptor-stimulated [35S]GTPgammaS binding: correlation with inhibition of guinea pig durai plasma protein extravasation. Eur J Pharmacol 1998; 352: 117–24PubMedCrossRefGoogle Scholar
  23. 23.
    Eglen RM, Jasper JR, Chang DA, et al. The 5-HT7 receptor: orphan found. Trends Pharmacol Sci 1997; 18: 104–7PubMedCrossRefGoogle Scholar
  24. 24.
    MacIntyre PD, Bhargava B, Hogg KJ, et al. Effect of subcutaneous sumatriptan, a selective 5HT1 agonist, on the systemic, pulmonary, and coronary circulation. Circulation 1993; 87: 401–5PubMedCrossRefGoogle Scholar
  25. 25.
    Tfelt-Hansen P, Sperling B, Winter PDO. Transient additional effect of sumatriptan on ergotamine-induced constriction of peripheral arteries in man. Clin Pharmacol Ther 1992; 51: 149Google Scholar
  26. 26.
    Dixon RM, Meire HB, Evans DH, et al. Peripheral vascular effects and pharmacokinetics of the antimigraine compound, zolmitriptan, in combination with oral ergotamine in healthy volunteers. Cephalalgia 1997; 17: 639–46PubMedCrossRefGoogle Scholar
  27. 27.
    Sciberras DG, Polvino WJ, Gertz BJ, et al. Initial human experience with MK-462 (rizatriptan): a novel 5-HT1d agonist. Br J Clin Pharmacol 1997; 43: 49–54PubMedCrossRefGoogle Scholar
  28. 28.
    De Vries P, Heiligers JPC, Villalón CM, et al. Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1d receptor antagonist. Br J Pharmacol 1996; 118: 85–92PubMedCrossRefGoogle Scholar
  29. 29.
    Pagniez F, Valentin JP, Vieu S, et al. Pharmacological analysis of the haemodynamic effects of 5-HT 1B/D receptor agonists in the normotensive rat. Br J Pharmacol 1998; 123: 205–14PubMedCrossRefGoogle Scholar
  30. 30.
    Willems E, De Vries P, Heiligers JP, et al. Porcine carotid vascular effects of eletriptan (UK-116,044): a new 5-HT1b/1d receptor agonist with anti-migraine activity. Naunyn Schmiedebergs Arch Pharmacol 1998; 358: 212–9PubMedCrossRefGoogle Scholar
  31. 31.
    Humphrey PP, Feniuk W, Perren MJ, et al. The pharmacology of the novel 5-HT1-like receptor agonist, GR 43175. Cephalalgia 1989; 9: 23–33PubMedGoogle Scholar
  32. 32.
    Dreteler GH, Wouters W, Saxena PR. Comparison of the cardiovascular effects of the 5-HTia receptor agonist flesinoxan with that of 8-OH-DPAT in the rat. Eur J Pharmacol 1990; 180: 339–49PubMedCrossRefGoogle Scholar
  33. 33.
    Friberg L, Olesen J, Iversen HK, et al. Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan. Lancet 1991; 338: 13–7PubMedCrossRefGoogle Scholar
  34. 34.
    Caekebeke JF, Ferrari MD, Zwetsloot CP, et al. Antimigraine drug sumatriptan increases blood flow velocity in large cerebral arteries during migraine attacks. Neurology 1992; 42: 1522–6PubMedCrossRefGoogle Scholar
  35. 35.
    Limmroth V, May A, Auerbach P, et al. Changes in cerebral blood flow velocity after treatment with sumatriptan or placebo and implications for the pathophysiology of migraine. J Neurol Sci 1996; 138: 60–5PubMedCrossRefGoogle Scholar
  36. 36.
    MacLennan SJ, Cambridge D, Whiting MV, et al. Cranial vascular effects of zolmitriptan, a centrally active 5-HT1B/1D receptor partial agonist for the acute treatment of migraine. Eur J Pharmacol 1998; 361: 191–7PubMedCrossRefGoogle Scholar
  37. 37.
    Shepheard SL, Williamson DJ, Baker R, et al. In vivo pharmacology of the novel 5-HT1d receptor agonist MK-462. Cephalalgia 1995; 15: 204Google Scholar
  38. 38.
    Gupta P, Brown D, Butler P, et al. Pre-clinical in vivo pharmacology of eletriptan (UK-116,044): a potent and selective partial agonist at ‘5-HT1D-like’ receptors. Cephalalgia 1996; 16: 386Google Scholar
  39. 39.
    Parsons AA, Parker SG, Raval P, et al. Comparison of the cardiovascular effects of the novel 5-HT(in1B/1Din)receptor agonist, SB 209509 (VML251), and sumatriptan in dogs. Cardiovasc Pharmacol 1997; 30: 136–41CrossRefGoogle Scholar
  40. 40.
    Sperling B, Tfelt-Hansen P, Lines C. Lack of effect of MK-462 on cerebral blood flow in humans. Cephalalgia 1995; 15: 206Google Scholar
  41. 41.
    De Vries P, Willems EW, Heiligers JPC, et al. Investigation of the role of 5-HT1b and 5-HT1d receptors in the sumatriptaninduced constriction of porcine carotid arteriovenous anastomoses. Br J Pharmacol 1999; 127: 405–12PubMedCrossRefGoogle Scholar
  42. 42.
    Heyck H. Pathogenesis of migraine. Res Clin Stud Headache 1969; 2: 1–28Google Scholar
  43. 43.
    Saxena PR. Cranial arteriovenous shunting, an in vivo animal model for migraine. In: Olesen J, et al. (editors). Experimental headache models. Philadelphia: Lippincott-Raven, 1995: 189–98Google Scholar
  44. 44.
    Van Es NM, Bruning TA, Camps J, et al. Assessment of peripheral vascular effects of antimigraine drugs in humans. Cephalalgia 1995; 15: 288–91PubMedCrossRefGoogle Scholar
  45. 45.
    Parsons AA, Raval P, Smith S, et al. Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries. J Cardiovasc Pharmacol 1998; 32: 220–4PubMedCrossRefGoogle Scholar
  46. 46.
    Martin GR. Inhibition of the trigemino-vascular system with 5-HT1dagonist drugs: selectively targeting additional sites of action. Eur Neurol 1996; 36: 13–8PubMedCrossRefGoogle Scholar
  47. 47.
    Gupta P, Napier CM, Scatchard J, et al. Further characterization of the in vitro pharmacology of eletriptan. Cephalalgia 1997; 17: 413CrossRefGoogle Scholar
  48. 48.
    Longmore J, Razzaque Z, Hargreaves RJ, et al. Rizatriptan selectively contracts human middle meningeal over coronary artery: comparison with sumatriptan. Cephalalgia 1997; 17: 388–9CrossRefGoogle Scholar
  49. 49.
    MaassenVanDenBrink A, Van Den Broek RWM, De Vries R, et al. Human middle meningeal and coronary artery contraction to eletriptan and sumatriptan. Cephalalgia 1999; 19: 398CrossRefGoogle Scholar
  50. 50.
    Van Den Broek RWM, MaassenVanDenBrink A, De Vries R, et al. Pharmacological analysis of contraction to eletriptan and sumatriptan in human isolated coronary artery and saphenous vein. Cephalalgia 1999; 19: 399Google Scholar
  51. 51.
    Gupta P, Scatchard J, Shepperson N, et al. In vitro pharmacology of eletriptan (UK-116,044) at the ‘5-HT1D-like’ receptor in the dog saphenous vein. Cephalalgia 1996; 16: 386Google Scholar
  52. 52.
    Beer MS, Middlemiss DN, Stanton JA, et al. In vitro pharmacological profile of the novel 5-HT1d receptor agonist MK-462. Cephalalgia 1995; 15: 203Google Scholar
  53. 53.
    MaassenVanDenBrink A, Reekers M, Bax WA, et al. Coronary side-effect potential of current and prospective antimigraine drugs. Circulation 1998; 98: 25–30PubMedCrossRefGoogle Scholar
  54. 54.
    Longmore J, Boulanger CM, Desta B, et al. 5-HT1d receptor agonists and human coronary artery reactivity in vitro: crossover comparisons of 5-HT and sumatriptan with rizatriptan and L-741, 519. Br J Clin Pharmacol 1996; 42: 431–41PubMedCrossRefGoogle Scholar
  55. 55.
    Connor HE, Feniuk W, Humphrey PPA. 5-Hydroxytryptamine contracts human coronary arteries predominantly via 5-HT2 receptor activation. Eur J Pharmacol 1989; 161: 91–4PubMedCrossRefGoogle Scholar
  56. 56.
    Bax WA, Renzenbrink GJ, Van Heuven-Nolsen D et al. 5-HT receptors mediating contractions of the isolated human coronary artery. Eur J Pharmacol 1993; 239: 203–10PubMedCrossRefGoogle Scholar
  57. 57.
    Shepheard SL, Williamson DJ, Beer MS, et al. Differential effects of 5-HT1b/1d receptor agonists on neurogenic durai plasma extravasation and vasodilation in anaesthetized rats. Neuropharmacology 1997; 36: 525–33CrossRefGoogle Scholar
  58. 58.
    Williamson DJ, Shepheard SL, Hill RG, et al. The novel antimigraine agent rizatriptan inhibits neurogenic durai vasodilation and extravasation. Eur J Pharmacol 1997; 328: 61–4PubMedCrossRefGoogle Scholar
  59. 59.
    Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993; 33: 48–56PubMedCrossRefGoogle Scholar
  60. 60.
    Goadsby PJ, Edvinsson L. Peripheral and central trigeminovascular activation in cat is blocked by the serotonin (5HT)-1d receptor agonist 311C 90. Headache 1994; 34: 394–9PubMedCrossRefGoogle Scholar
  61. 61.
    Shepheard SL, Williamson DJ, Williams J, et al. Comparison of the effects of sumatriptan and the NK1antagonist CP-99,994 on plasma extravasation in dura mater and c-fos mRNA expression in trigeminal nucleus caudalis of rats. Neuropharmacology 1995; 34: 255–61PubMedCrossRefGoogle Scholar
  62. 62.
    Goadsby PJ, Hoskin KL. Inhibition of trigeminal neurons by intravenous administration of the serotonin (5HT)1B/Dreceptor agonist zolmitriptan (311C90): are brain stem sites therapeutic target in migraine? Pain 1996; 67: 355–9PubMedCrossRefGoogle Scholar
  63. 63.
    Cumberbatch MJ, Hill RG, Hargreaves RJ. The effects of 5-HT1a, 5-HT1b and 5-HT1d receptor agonists on trigeminal nociceptive neurotransmission in anaesthetized rats. Eur J Pharmacol 1998; 362: 43–6PubMedCrossRefGoogle Scholar
  64. 64.
    Goadsby PJ, Knight Y. Inhibition of trigeminal neurones after intravenous administration of naratriptan through an action at 5-hydroxytryptamine (5-HT1b/1D) receptors. Br J Pharmacol 1997; 122: 918–22PubMedCrossRefGoogle Scholar
  65. 65.
    Cumberbatch MJ, Hill RG, Hargreaves RJ. Rizatriptan has central antinociceptive effects against durally evoked responses. Eur J Pharmacol 1997; 328: 37–40PubMedCrossRefGoogle Scholar
  66. 66.
    Yu XJ, Waeber C, Castanon N, et al. 5-Carboxamido-tryptamine, CP-122,288 and dihydroergotamine but not sumatriptan, CP-93,129, and serotonin-5-O-carboxymethyl-glycyl-tyrosinamide block durai plasma protein extravasation in knockout mice that lack 5-hydroxytryptamine1B receptors. Mol Pharmacol 1996; 49: 761–5PubMedGoogle Scholar
  67. 67.
    Yu XJ, Cutrer FM, Moskowitz MA, et al. The 5-HT1D receptor antagonist GR-127,935 prevents inhibitory effects of sumatriptan but not CP-122,288 and 5-CT on neurogenic plasma extravasation within guinea pig dura mater. Neuropharmacology 1997; 36: 83–91PubMedCrossRefGoogle Scholar
  68. 68.
    Phebus LA, Johnson KW, Zgombick JM, et al. Characterization of LY344864 as a pharmacological tool to study 5-HT1f receptors: binding affinities, brain penetration and activity in the neurogenic durai inflammation model of migraine. Life Sci 1997; 61: 2117–26PubMedCrossRefGoogle Scholar
  69. 69.
    Johnson KW, Schaus JM, Durkin MM, et al. 5-HT1F receptor agonists inhibit neurogenic durai inflammation in guinea pigs. Neuroreport 1997; 8: 2237–40PubMedCrossRefGoogle Scholar
  70. 70.
    Roon K, Diener HC, Ellis P, et al. CP-122,287 blocks neurogenic inflammation, but is not effective in aborting migraine attacks: results of two controlled clinical trials. Cephalalgia 1997; 17: 245Google Scholar
  71. 71.
    May A, Shepheard SL, Knorr M, et al. Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology of migraine. Brain 1998; 121: 1231–7PubMedCrossRefGoogle Scholar
  72. 72.
    Mills A, Rhodes P, Martin GR. [3H]311C90 binding sites in cat brain stem: implications for migraine treatment. Cephalalgia 1995; 15: 116Google Scholar
  73. 73.
    Moskowitz MA. Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. Trends Pharmacol Sci 1992; 13: 307–11PubMedCrossRefGoogle Scholar
  74. 74.
    Goadsby PJ. Current concepts of the pathophysiology of migraine. Neurol Clin 1997; 15: 27–42PubMedCrossRefGoogle Scholar
  75. 75.
    Saxena PR, Tfelt-Hansen P. Triptans, 5-HT1b/1d receptor agonists in the acute treatment of migraine. In: Olesen J, et al. (editors). The headaches. Philadelphia: Lippincott, Williams &Wilkins, 2000:411–38Google Scholar
  76. 76.
    Saxena PR, Ferrari MD. 5-HT1-like receptor agonists and the pathophysiology of migraine. Trends Pharmacol Sci 1989; 10: 200–4PubMedCrossRefGoogle Scholar
  77. 77.
    Ferrari MD, Saxena PR. Clinical and experimental effects of sumatriptan in humans. Trends Pharmacol Sci 1993; 14: 129–33PubMedCrossRefGoogle Scholar
  78. 78.
    Humphrey PPA, Goadsby PJ. The mode of action of sumatriptan is vascular? A debate. Cephalalgia 1994; 14: 401–10PubMedCrossRefGoogle Scholar
  79. 79.
    Goadsby PJ, Zagami AS, Lambert GA. Neural processing of craniovascular pain: a synthesis of the central structures involved in migraine. Headache 1991; 31: 365–71PubMedCrossRefGoogle Scholar
  80. 80.
    Cutler NR, Gomez-Mancilla B, Lebowitz M, et al. A study of safety and efficacy in patients with acute migraine, using PNU-142633, a selective 5-HT1D agonist. Cephalalgia 2000; 20: 268CrossRefGoogle Scholar
  81. 81.
    Fowler PA, Lacey LF, Thomas M, et al. The clinical pharmacology, pharmacokinetics and metabolism of sumatriptan. Eur Neurol 1991; 31: 291–94PubMedCrossRefGoogle Scholar
  82. 82.
    Duquesnoy C, Mamet JP, Sumner D, et al. Comparative clinical pharmacokinetics of single doses of sumatriptan following subcutaneous, oral, rectal and intranasal administration. Eur J Pharm Sci 1998; 6: 99–104PubMedCrossRefGoogle Scholar
  83. 83.
    Lacey LF, Hussey EK, Fowler PA. Single dose pharmacokinetics of sumatriptan in healthy volunteers. Eur J Clin Pharmacol 1995; 47: 543–8PubMedCrossRefGoogle Scholar
  84. 84.
    Kunka RL, Hussey EK, Shaw S, et al. Safety, tolerability, and pharmacokinetics of sumatriptan suppositories following single and multiple doses in healthy volunteers. Cephalalgia 1997; 17:532–40PubMedCrossRefGoogle Scholar
  85. 85.
    Seaber EJ, Peck RW, Smith DA, et al. The absolute bioavailability and effect of food on the pharmacokinetics of zolmitriptan in healthy volunteers. Br J Clin Pharmacol 1998; 46: 433–9PubMedCrossRefGoogle Scholar
  86. 86.
    Peck RW, Seaber EJ, Dixon RM, et al. The pharmacodynamics and pharmacokinetics of the 5HT1B/1D-agonist zolmitriptan in healthy young and elderly men and women. Clin Pharmacol Ther 1998; 63: 342–53PubMedCrossRefGoogle Scholar
  87. 87.
    Kempsford RD, Baille P, Fuseau E. Oral naratriptan (2.5–10 mg) exhibit dose-proportional pharmacokinetics. Cephalalgia 1997; 17: 408Google Scholar
  88. 88.
    Fuseau E, Baille P, Kempsford RD. A study to determine the absolute oral bioavailability of naratriptan. Cephalalgia 1997; 17: 417Google Scholar
  89. 89.
    Goldberg MR, Lee Y, Vyas KP, et al. Rizatriptan, a novel 5-HT1B/1D agonist for migraine: single-and multiple-dose tolerability and pharmacokinetics in healthy subjects. J Clin Pharmacol 2000; 40: 74–83PubMedCrossRefGoogle Scholar
  90. 90.
    Cheng H, Polvino WJ, Sciberras D, et al. Pharmacokinetics and food interaction of MK-462 in healthy males. Biopharm Drug Dispos 1996; 17: 17–24PubMedCrossRefGoogle Scholar
  91. 91.
    Milton KA, Buchanan TJ, Haug-Pihale G, et al. The pharmacokinetics, safety and tolerability of oral eletriptan in subjects with impaired hepatic function. Cephalalgia 1998; 18: 411–2Google Scholar
  92. 92.
    Hyland R, Jones BC, McCleverty P, et al. In vitro metabolism of eletriptan in human liver microsomes. Cephalalgia 1998; 18: 404Google Scholar
  93. 93.
    Morgan P, Rance D, James G, et al. Comparative absorption and elimination of eletriptan in rat, dog and human. Cephalalgia 1997; 17: 414Google Scholar
  94. 94.
    Robert M, Warrington SJ, Zayas JM, et al. Electrocardiographic effects and pharmacokinetics of oral almotriptan in healthy subjects. Cephalalgia 1998; 18: 406Google Scholar
  95. 95.
    Cabaroccas X, Salva M. Pharmacokinetic and metabolic data on almotriptan, a new antimigraine drug. Cephalalgia 1997; 17: 421Google Scholar
  96. 96.
    Fernandez FJ, Cabaroccas X, Zayas JM, et al. Oral almotriptan in the treatment of migraine. A dose finding study. Cephalalgia 1999; 19: 362–3Google Scholar
  97. 97.
    Buchan P. The pharmacokinetics of frovatriptan (VML 251/SB 209509), a potent selective 5-HT1b/1dagonist, following single dose administration by oral and intravenous routes to healthy male and female volunteers. Headache 1998; 38: 376Google Scholar
  98. 98.
    Rance D, Clear N, Dallman L. Physicochemical comparison of eletriptan and other 5-HT1D-like agonists as a predictor of oral absoption potential. Headache 1997; 37: 328Google Scholar
  99. 99.
    Moore KHP, Hussey EK, Shaw S, et al. Safety, tolerability, and pharmacokinetics of sumatriptan in healthy subjects following ascending single intranasal doses and multiple intranasal doses. Cephalalgia 1997; 17: 541–50PubMedCrossRefGoogle Scholar
  100. 100.
    Dixon R, On N, Posner J. High oral bioavailability of the novel 5-HT1d agonist 311C 90. Cephalalgia 1995; 15: 218Google Scholar
  101. 101.
    Dixon R, Gillotin C, Gibbens M, et al. The pharmacokinetics and effects on blood pressure of multiple doses of the novel anti-migraine drug zolmitriptan (311C90) in healthy volunteers. Br J Clin Pharmacol 1997; 43: 273–81PubMedCrossRefGoogle Scholar
  102. 102.
    Rolan PE, Martin GR. Zolmitriptan: a new acute treatment for migraine. Exp Opin Invest Drugs 1998; 7: 633–52CrossRefGoogle Scholar
  103. 103.
    Kempsford RD, Nicholls B, Lam R, et al. A study to investigate the potential interaction of naratriptan and ergotamine. Cephalalgia 1997; 17: 416Google Scholar
  104. 104.
    Kempsford RD, Nicholls B, Lam R, et al. A study to investigate the potential interaction of naratriptan and dihydroergotamine. Cephalalgia 1997; 17: 416Google Scholar
  105. 105.
    Dahlöf C, Lines C. Rizatriptan: a new 5-HT1B/1Dreceptor agonist for the treatment of migraine. Exp Opin Invest Drugs 1999; 8: 671–86CrossRefGoogle Scholar
  106. 106.
    Goldberg MR, Lowry RC, Musson DG. Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine. Br J Clin Pharmacol 1999; 39: 1–8Google Scholar
  107. 107.
    Geraud G, Olesen J, Pfaffenrath V, et al. Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design. Cephalalgia 2000; 20: 30–8PubMedCrossRefGoogle Scholar
  108. 108.
    Gallagher RM. Comparison of zolmitriptan and sumatriptan for the acute treatment of migraine. Cephalalgia 1999; 19: 358Google Scholar
  109. 109.
    Diener HC, Pascual J, Vega P. Comparison of rizatriptan 10 mg versus zolmitriptan 2.5 mg in migraine. Headache 1999; 39: 351Google Scholar
  110. 110.
    Havana H, Dahlof C, Pop PH, et al. Efficacy of naratriptan tablets in the acute treatment of migraine: a dose-ranging study: Naratriptan S2WB2004 Study Group. Clin Ther 2000; 22: 970–80CrossRefGoogle Scholar
  111. 111.
    Bates D, Winter P. Efficacy and tolerability of naratriptan tablets (0.1–2.5 mg) in the acute treatment of migraine. Eur J Neurol 1998; 5: S48–S9Google Scholar
  112. 112.
    Göbel H, Winter P, Boswell D, et al. Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients: Naratriptan International Recurrence Study Group. Clin Ther 2000; 22: 981–9PubMedCrossRefGoogle Scholar
  113. 113.
    Bornhof MK, Legg N, Paz J. Comparison of rizatriptan 10 mg vs naratriptan 2.5 mg in migraine. Headache 1999; 39: 344Google Scholar
  114. 114.
    Visser WH, Terwindt GM, Reines SA, et al. Rizatriptan vs sumatriptan in the acute treatment of migraine. A placebo-controlled, dose-ranging study. Arch Neurol 1996; 53: 1132–7Google Scholar
  115. 115.
    Lines C, Visser WH, Vandormael K, et al. Rizatriptan 5 mg versus sumatriptan 50 mg in the acute treatment of migraine. Headache 1997; 37: 319–20Google Scholar
  116. 116.
    Goldstein J, Ryan R, Jiang K, et al. Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Headache 1998; 38: 737–47PubMedCrossRefGoogle Scholar
  117. 117.
    Tfelt-Hansen P, Teall J, Rodriguez F, et al. Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Headache 1998; 38: 748–55PubMedCrossRefGoogle Scholar
  118. 118.
    Jackson NC, on behalf of the Eletriptan Steering Committee. Clinical measures of efficacy, safety and tolerability for the acute treatment of migraine: a comparison of eletriptan (20–80 mg), sumatriptan (100 mg) and placebo. Neurology 1998; 50: A376CrossRefGoogle Scholar
  119. 119.
    Pitman V, Forster E, Jackson N. Comparison of the efficacy of oral eletriptan and oral sumatriptan for the acute treatment of migraine: combined analysis across three clinical trials. Headache 1999; 39: 374Google Scholar
  120. 120.
    Cabarrocas X, Zayas JM, Suris M, et al. Equivalent efficacy of oral almotriptan, a new 5-HT1b/1d agonist, compared with sumatriptan 100 mg. Headache 1998; 38: 377–8Google Scholar
  121. 121.
    Dahlöf C, Hogenhuis L, Olesen J, et al. Early clinical experience with subcutaneous naratriptan in the acute treatment of migraine: a dose-ranging study. Eur J Neurol 1998; 5: 469–77PubMedCrossRefGoogle Scholar
  122. 122.
    Multinational Oral Sumatriptan and Cafergot Comparative Study Group. A randomized, double-blind comparison of sumatriptan in the acute treatment of migraine. Eur Neurol 1991; 31: 314–22CrossRefGoogle Scholar
  123. 123.
    Oral Sumatriptan and Aspirin plus Metoclopramide Comparative Study Group. A study to compare oral sumatriptan with oral aspirin plus oral metoclopramide in the acute treatment of migraine. Eur Neurol 1992; 32: 177–84CrossRefGoogle Scholar
  124. 124.
    Tfelt-Hansen P, Henry P, Mulder K, et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet 1995; 346: 923–6PubMedCrossRefGoogle Scholar
  125. 125.
    Myllylä V, Havanka H, Herrala L, et al. Tolfenamic acid rapid release versus sumatriptan in the acute treatment of migraine: comparable effect in a double-blind, randomized, controlled, parallel-group study. Headache 1998; 38: 201–7PubMedCrossRefGoogle Scholar
  126. 126.
    The Diclofenac-K/Sumatriptan Migraine Study Group. Acute treatment of migraine attacks: efficacy and safety of a nonsteroidal anti-inflammatory drug, diclofenac-potassium, in comparison to oral sumatriptan and placebo. Cephalalgia 1999; 19: 232–40CrossRefGoogle Scholar
  127. 127.
    Touchon J, Bertin L, Pilgrim AJ, et al. Acomparison of subcutaneous sumatriptan and dihydroergotamine nasal spray in the acute treatment of migraine. Neurology 1996; 47: 361–5PubMedCrossRefGoogle Scholar
  128. 128.
    Winner P, Ricalde O, Le Force B, et al. A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine. Arch Neurol 1996; 53: 180–4PubMedCrossRefGoogle Scholar
  129. 129.
    Diener HC. for the ASASUMAMIG Study Group. Efficacy and safety of intravenous acerylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine. A double-blind, double-dummy, randomized, parallel group study. Cephalalgia 1999; 19: 581–8Google Scholar
  130. 130.
    Boureau F, Kappos L, Schoenen J, et al. A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine. Int J Clin Pract 2000; 54: 281–6PubMedGoogle Scholar
  131. 131.
    Swedish Medical Products Agency. Monography on sumatriptan suppositories [online]. Available from: http://www.mpa.se/lakemedel/nnlakeindex.html [Accessed 2000 Oct 24]
  132. 132.
    Reches A, on behalf of the Eletriptan Steering Committee. Comparison of the efficacy, safety and tolerability of oral eletriptan and Cafergot® for the acute treatment of migraine. Cephalalgia 1999; 19: 355Google Scholar
  133. 133.
    Tfelt-Hansen P. Efficacy and adverse events of subcutaneous, oral, and intranasal sumatriptan used for migraine treatment: a systemic review based on number needed to treat. Cephalalgia 1998; 18: 532–8PubMedCrossRefGoogle Scholar
  134. 134.
    Cady RK, Wendt JK, Kirchner JR, et al. Treatment of acute migraine with subcutaneous sumatriptan. JAMA 1991; 265: 2831–5PubMedCrossRefGoogle Scholar
  135. 135.
    Subcutaneous Sumatriptan International Study Group. Treatment of migraine attacks with sumatriptan. N Engl J Med 1991; 325: 316–21CrossRefGoogle Scholar
  136. 136.
    Sumatriptan Auto-Injector Study Group. Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device. Eur Neurol 1991; 31: 323–31CrossRefGoogle Scholar
  137. 137.
    Gross MLP, Kay J, Turner AM, et al. Sumatriptan in acute migraine using a novel cartridge system self-injector. Headache 1994; 34: 559–63PubMedCrossRefGoogle Scholar
  138. 138.
    Jensen K, Tfelt-Hansen P, Hansen EW, et al. Introduction of a novel self-injector for sumatriptan. A controlled clinical trial in general practice. Cephalalgia 1995; 15: 423–9Google Scholar
  139. 139.
    Bousser MG, d’Allens H, Richard A, et al. Efficacy of subcutaneous sumatriptan in the acute treatment of early-morning migraine: a placebo-controlled study. J Intern Med 1993; 234: 211–6PubMedCrossRefGoogle Scholar
  140. 140.
    Henry P, d’ Allens H, and the French Migraine Network Bordeaux-Lyon-Grenoble. Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. Headache 1993; 33: 432–5PubMedCrossRefGoogle Scholar
  141. 141.
    Mathew NT, Dexter J, Couch J, et al. Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. Arch Neurol 1992; 49: 1271–6PubMedCrossRefGoogle Scholar
  142. 142.
    Russel MB, Holm-Thomsen OE, Nielsen MR, et al. A randomized, double-blind, placebo-controlled crossover study of subcutaneous sumatriptan in general practice. Cephalalgia 1994; 14: 291–6CrossRefGoogle Scholar
  143. 143.
    Facchinetti F, Bonellie G, Kangasneimi P, et al. The efficacy and safety of sumatriptan in the acute treatment of menstrual migraine. Obstet Gynecol 1995; 86: 911–6PubMedCrossRefGoogle Scholar
  144. 144.
    Mushet GR, Cady RK, Baker CC, et al. Efficacy and tolerability of of subcutaneous sumatriptan administered using the IM-ITREX®_STATdose™ system. Clin Ther 1996; 18: 687–99PubMedCrossRefGoogle Scholar
  145. 145.
    Cady RC, Ryan R, Jhingran P, et al. Sumatriptan injection reduces productivity loss during a migraine attack. Results of a double-blind, placebo-controlled trial. Arch Intern Med 1998; 158: 1013–8Google Scholar
  146. 146.
    Akpunonu BE, Mutgi AB, Federman DJ, et al. Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study. Ann Emerg Med 1995; 25: 464–9PubMedCrossRefGoogle Scholar
  147. 147.
    Cady RK, Dexter J, Sargent JD, et al. Efficacy of subcutaneous sumatriptan in repeated episodes of migraine. Neurology 1993; 43: 1363–8PubMedCrossRefGoogle Scholar
  148. 148.
    Pfaffenrath V, Cunin G, Sjonell G, et al. Efficacy and safety of sumatriptan tablets (25mg, 50mg, 100mg) in the acute treatment of migraine: defining the optimum doses of oral sumatriptan. Headache 1998; 38: 184–90PubMedCrossRefGoogle Scholar
  149. 149.
    Oral Sumatriptan Dose-defining Study Group. Sumatriptan — an oral dose-defining study. Eur Neurol 1991; 31: 300–5CrossRefGoogle Scholar
  150. 150.
    Oral Sumatriptan International Multiple-Dose Study Group. Evaluation of a multiple-dose regimen of oral sumatriptan for the acute treatment of migraine. Eur Neurol 1991; 31: 306–13CrossRefGoogle Scholar
  151. 151.
    Goadsby PJ, Zagami AS, Donnan GA, et al. Oral sumatriptan in acute migraine. Lancet 1991; 338: 782–3PubMedCrossRefGoogle Scholar
  152. 152.
    Cutler N, Mushet GR, Davis R, et al. Oral sumatriptan for the acute treatment of migraine: Evaluation of three dosage strengths. Neurology 1995; 45: S5–S9PubMedGoogle Scholar
  153. 153.
    Sargent J, Kirchner JR, Davis R, et al. Oral sumatriptan is effective and well tolerated for the acute treatment of migraine: Results of a multicenter study. Neurology 1995; 45: S10–S14PubMedGoogle Scholar
  154. 154.
    Nappi G, Sicuteri F, Byrne M, et al. Oral sumatriptan compared with placebo in the acute treatment of migraine. J Neurol 1994; 41: 138–44Google Scholar
  155. 155.
    Rederich G, Rapoport A, Cutler N et al. Oral sumatriptan for the long-term treatment of migraine: clinical findings. Neurology 1995; 45: S15–S20PubMedCrossRefGoogle Scholar
  156. 156.
    Savani N, Brautaset NJ, Reunanen M, et al. A double-blind placebo-controlled study assessing the efficacy and tolerability of sumatriptan 50-mg tablets in the acute treatment of migraine. Int J Clin Pract 1999; Suppl. 105: 7–15Google Scholar
  157. 157.
    Salonen R, Ashford EA, Hassani H. and The S2BM11 Study Group. Patients preference for oral sumatriptan 25, 50 or 100 mg in the acute treatment of migraine: a double-blind, randomized, crossover study. Int J Clin Pract 1999; Suppl. 105: 16–24PubMedGoogle Scholar
  158. 158.
    Salonen R, Asford E, Dahlöf C, et al. Intranasal sumatriptan for the acute treatment of migraine. J Neurol 1994; 241: 463–9PubMedCrossRefGoogle Scholar
  159. 159.
    Dahlöf C. Sumatriptan nasal spray: a review of data from multinational clinical trials. Funct Neurol 1996; 11: 150Google Scholar
  160. 160.
    Ryan R, Elkind A, Baker CC, et al. Sumatriptan nasal spray for the acute treatment of migraine. Results of two clinical studies. Neurology 1997; 49: 1225–30Google Scholar
  161. 161.
    Diamond S, Elkind A, Jackson T, et al. Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine. Arch Fam Med 1998; 7: 234–40PubMedCrossRefGoogle Scholar
  162. 162.
    Peikert A, Becker WJ, Ashford EA, et al. Sumatriptan nasal spray: a dose-ranging study in the acute treatment of migraine. Eur J Neurol 1999; 6: 43–9PubMedCrossRefGoogle Scholar
  163. 163.
    Ashford E, Salonen R, Saiers J, et al. Consistency of response to sumatriptan nasal spray across patient subgroups and migraine types. Cephalalgia 1998; 18: 273–7PubMedCrossRefGoogle Scholar
  164. 164.
    Swedish Medical Products Agency. Monograph on sumatriptan nasal spray. Available from: http://www.mpa.se/lakemedel/nn_lakeindex.html [Accessed 2000 Oct 24]
  165. 165.
    Tepper SJ, Cochran A, Hobbs S, et al. Sumatriptan suppositories for the acute treatment of migraine. Int J Clin Pract 1998; 52: 31–5PubMedGoogle Scholar
  166. 166.
    Göbel H, on behalf on the Study Group. A placebo-controlled, dose-defining study of sumatriptan suppositories in the acute treatment of migraine. In: Olesen J, et al. (editors). Headache treatment: trial methodology and new drugs. Philadelphia: Lippincott-Raven, 1997: 203–6Google Scholar
  167. 167.
    Henriksson A, on behalf of the Study Group. Safety and efficacy of sumatriptan suppositories in the acute treatment of migraine attacks. Cephalalgia 1995; 15: 235Google Scholar
  168. 168.
    Klassen AC, Gabriel H, Hobbs S, et al. Safety and efficacy of sumatriptan suppositories in the acute treatment of migraine attacks. Cephalalgia 1995; 15: 234Google Scholar
  169. 169.
    Ferrari MD, James MH, Bates D, et al. Oral sumatriptan: effect of a second dose, and treatment of headache recurrence. Cephalalgia 1994; 14: 330–8PubMedCrossRefGoogle Scholar
  170. 170.
    Scott RJ, Aitchison WRC, Barker PR, et al. Oral sumatriptan in the acute treatment of migraine and migraine recurrence in general practice. Q J Med 1996; 89: 613–22CrossRefGoogle Scholar
  171. 171.
    Visser WH, de Vriend RH, Jaspers MW, et al. Sumatriptan in clinical practice: a 2-year review of 453 migraine patients. Neurology 1996; 47: 46–51PubMedCrossRefGoogle Scholar
  172. 172.
    Rapoport A, Visser WH, Cutler NR, et al. Oral sumatriptan in preventing headache recurrence after treatment of migraine attacks with subcutaneous sumatriptan. Neurology 1995; 45: 1505–9PubMedCrossRefGoogle Scholar
  173. 173.
    Cull RE, Price WH, Dunbar A. The efficacy of subcutaneous sumatriptan in the treatment of recurrence of migraine headache. J Neurol Neurosurg Psychiat 1997; 62: 490–5PubMedCrossRefGoogle Scholar
  174. 174.
    Bates D, Ashford E, Dawson R, et al. Subcutaneous sumatriptan during migraine aura. Neurology 1994; 44: 1587–92PubMedCrossRefGoogle Scholar
  175. 175.
    Schoenen J, Sawyer J. Zolmitriptan (Zornig™, 311C90), a novel dual central and peripheral 5HT1b/1d agonist: an overview of efficacy. Cephalalgia 1997; 17: 28–40PubMedGoogle Scholar
  176. 176.
    Ferrari MD. 311C90: Increasing the options for therapy with effective acute antimigraine 5HT1B/1D receptor agonists. Neurology 1997; 48: S21–S4PubMedCrossRefGoogle Scholar
  177. 177.
    Solomon GD, Cady RK, Klapper JA, et al. The clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. Neurology 1997; 49: 1219–25PubMedCrossRefGoogle Scholar
  178. 178.
    Visser WH, Klein KB, Cox RC, et al. 311C90, a new central and peripherally acting 5-HTiD receptor agonist in the acute oral treatment of migraine: a double-blind, placebo-controlled, dose-range finding study. Neurology 1996; 46: 522–6PubMedCrossRefGoogle Scholar
  179. 179.
    Rapoport AM, Ramadan NM, Adelman JU, et al. Optimizing the dose of zolmitriptan (ZomigTM, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. Neurology 1997; 49: 1210–8Google Scholar
  180. 180.
    Dahlöf C, Diener H-C, Goadsby PJ, et al. Zolmitriptan, a 5-HT receptor agonist for the acute oral treatment of migraine: a multicentre, dose-range finding study. Eur J Neurol 1998; 5: 535–43PubMedCrossRefGoogle Scholar
  181. 181.
    Mathew NT, Asgharnejad M, Peykamian M, et al. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled crossover study. Neurology 1997; 49: 1485–90Google Scholar
  182. 182.
    Klassen A, Elkind A, Asgharnejad M, et al. Naratriptan is effective and well-tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, parallel-group study. Headache 1997; 37: 640–5Google Scholar
  183. 183.
    Gunasekara NS, Wiseman LR. Naratriptan. CNS Drugs 1997; 8: 402–8CrossRefGoogle Scholar
  184. 184.
    Gijsman H, Kramer MS, Sargent J, et al. Double-blind, placebo-controlled, dose-finding study of rizatriptan (MK-462) in the acute treatment of migraine. Cephalalgia 1997; 17: 547–651Google Scholar
  185. 185.
    Teall J, Tuchman M, Cutler N, et al. Rizatriptan (MAXALT®) for the acute treatment of migraine and migraine recurrence. Headache 1998; 38: 281–7PubMedCrossRefGoogle Scholar
  186. 186.
    Kramer M, Matzura-Wolfe D, Polis A, et al. A placebo-controlled crossover study of rizatriptan in the treatment of multiple attacks. Neurology 1998; 51: 773–81PubMedCrossRefGoogle Scholar
  187. 187.
    Ahrens SP, Visser WH, Jiang K, et al. Rizatriptan RPD™ for the acute treatment of migraine. Eur J Neurol 1998; 5: S52Google Scholar
  188. 188.
    Färkkilä M, Diener H-C, Dahlöf C, et al. A dose-finding study of eletriptan (UK-116,044) (5–30 mg) for the acute treatment of migraine. Cephalalgia 1996; 16: 387Google Scholar
  189. 189.
    Hettiarachichi J, on behalf of the Eletriptan Steering Committee. Efficacy, safety and tolerability of oral eletriptan versus placebo in the acute treatment of migraine: a phase III randomised trial. Headache 1999; 39: 358–9Google Scholar
  190. 190.
    Hettiarachichi J, on behalf of the Eletriptan Steering Committee. Adverse event profile of oral eletriptan: review of clinical trial experience. Cephalalgia 1999; 19: 355Google Scholar
  191. 191.
    Cabarrocas X, on behalf of the Almotriptan Subcutaneous Study Group. First efficacy data on subcutaneous almotriptan, a novel 5HT1Dagonist. Cephalalgia 1997; 17: 420–1Google Scholar
  192. 192.
    Martinez E, Cabarrocas X, Peris F, et al. Meta-analysis of the efficacy and safety of almotriptan in the treatment of migraine. Cephalalgia 1999; 19: 362Google Scholar
  193. 193.
    Cabarrocas X, on behalf of the Almotriptan Oral Study Group. Efficacy data on oral almotriptan, a novel 5HT1B/1Dagonist. Headache 1998; 38: 377Google Scholar
  194. 194.
    Ryan R, Key wood C, on behalf of the US Multi-center Study ofVML 251. A preliminary study of VML251 (SB209509) a novel 5HT1B/1Dagonist for the treatment of migraine attacks. Cephalalgia 1997; 17: 418Google Scholar
  195. 195.
    Goldstein J, Keywood C. A low dose range finding study of frovatriptan, a potent selective 5-HT1B/1Dagonist for the treatment of migraine. Funct Neurol 1998; 13: 178Google Scholar
  196. 196.
    Tansey MJB, Pilgrim AJ, Martin PM. Long-term experience with sumatriptan in the treatment of migraine. Eur Neurol 1993; 33: 310PubMedCrossRefGoogle Scholar
  197. 197.
    Gross MLP, Kay J, Turner AM, et al. Long-term efficacy of subcutaneous sumatriptan using a novel self-injector. Headache 1995; 35: 601–6PubMedCrossRefGoogle Scholar
  198. 198.
    The International 311C90 Long-term Study Group. The long-term tolerability and efficacy of oral zolmitriptan (Zomig, 311C90) in the acute treatment of migraine. An international study. Headache 1998; 38: 173–83CrossRefGoogle Scholar
  199. 199.
    Bomhof MAM, Heywood J, Pradalier A, et al. The tolerability and efficacy of naratriptan tablets with long-term treatment (6 months). Cephalalgia 1998; 18: 33–7PubMedCrossRefGoogle Scholar
  200. 200.
    Block GA, Goldstein J, Polis A, et al. Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Headache 1998; 38: 764–71PubMedCrossRefGoogle Scholar
  201. 201.
    Tfelt-Hansen P. Pitfalls in long-term studies assessing acute migraine therapy. Cephalalgia. in pressGoogle Scholar
  202. 202.
    Massiou H, Tzourio C, El Amrani M, et al. Verbal scales in the acute treatment of migraine: semantic categories and clinical relevance. Cephalalgia 1997; 17: 37–9PubMedCrossRefGoogle Scholar
  203. 203.
    Ferrari MD. How to assess and compare drugs in the management of migraine: success rates in term of response and recurrence. Cephalalgia 1999; 19: 2–8PubMedGoogle Scholar
  204. 204.
    Tfelt-Hansen P, Eickhoff JH, Olesen J. The effect of single dose ergotamine tartrate on peripheral arteries in migraine patients: methodological aspects and time effect curve. Acta Pharmacol Toxicol 1980; 47: 151–6CrossRefGoogle Scholar
  205. 205.
    Aellig WH, Rosenthaler J. Venoconstrictor effects of dihydro-ergotamine after intranasal and intramuscular administration. Eur J Clin Pharmacol 1986; 30: 581–4PubMedCrossRefGoogle Scholar
  206. 206.
    Göbel H, Petersen-Braun M, Heinze A. Which properties do patients expect of new and improved drugs in the treatment of primary headache disorders? In: Olesen J, et al. (editors). Headache treatment: trial methodology and new drugs. Philadelphia: Lippincott-Raven, 1997: 93–7Google Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Peer Tfelt-Hansen
    • 1
  • Peter De Vries
    • 2
  • Pramod R. Saxena
    • 2
  1. 1.Department of Neurology, Glostrup HospitalUniversity of CopenhagenGlostrupDenmark
  2. 2.Department of Pharmacology, Dutch Migraine Research Group and Cardiovascular Research Institute ‘ COEUR’Erasmus University Medical Centre ‘EMRCRotterdamThe Netherlands
  3. 3.Department of NeurologyGlostrup HospitalGlostrupDenmark

Personalised recommendations