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, alpha 1-adrenergic, alpha 2-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.(ABSTRACT TRUNCATED AT 250 WORDS)