Journal of Neurology

, Volume 238, Supplement 1, pp S45–S52 | Cite as

5-HT2 receptor antagonists and migraine therapy

  • E. J. Mylecharane
Migraine Therapy And 5-HT Receptor Activity


5-Hydroxytryptamine (5-HT; serotonin) has been implicated in the pathophysiology of migraine, and several drugs with potent 5-HT2 receptor blocking activity (methysergide, pizotifen, cyproheptadine and mianserin) have been recognized as being clinically effective in migraine prophylaxis, although the selective 5-HT2 receptor antagonist ketanserin (the principal agent used to identify 5-HT2 receptor-mediated actions) seems to be ineffective in migraine. Pizotifen is the most widely used 5-HT2 receptor antagonist in migraine prophylaxis, because of its superior efficacy compared with cyproheptadine, and because the incidence and severity of adverse effects with pizotifen is lower compared with methysergide and mianserin. These agents have additional antagonistic effects at histamine H1, muscarinic cholinergic, α1-adrenergic, α2-adrenergic and dopamine receptors, but drugs which are selective for these non-5-HT receptors appear to be of no benefit in migraine. Actions mediated by 5-HT2 receptors which could be of relevance to migraine comprise cranial vasoconstriction, increased cranial capillary permeability and platelet aggregation, and some central nervous system effects and neuroendocrine functions. Although pizotifen, cyproheptadine and mianserin are considered to be relatively specific for 5-HT2 receptors, these agents and methysergide all share a high affinity for 5-HT1C binding sites; ketanserin, however, has little affinity for these sites, thus activation of 5-HT1C receptors may be an important step in the pathogenesis of migraine. It is not yet known which 5-HT1C receptor-mediated actions of 5-HT are relevant to migraine, but some behavioural actions and cranial vasodilatation via release of endothelium-derived relaxing factor may be involved. If 5-HT1C rather than 5-HT2 receptor-mediated actions are important, then other 5-HT2 receptor antagonists with a high affinity at 5-HT1C binding sites, such as LY 53857, metergoline, mesulergine, ritanserin and SCH 23390, may also prove to be effective in migraine. The efficacy of methysergide may also depend on other 5-HT1-like receptor-mediated actions such as cranial vasoconstriction, and inhibition of cranial vascular neurogenic inflammation. The efficacy of these agents implies that 5-HT is causally involved in at least some of the underlying pathophysiology of migraine.

Key words

5-HT2 receptor antagonists Migraine therapy Cranial vascular actions CNS actions 5-HT1C receptors 


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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • E. J. Mylecharane
    • 1
  1. 1.Department of PharmacologyUniversity of SydneyAustralia

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