title: 5-HT3 receptor antagonists and migraine therapy.
abstract: Neuronal 5-hydroxytryptamine3 (5-HT3) receptors mediate the excitatory effects of 5-HT. They are located in pain- and nausea-modulating areas in the central nervous system and on C-fibre primary afferents in the peripheral nervous system. Consequently, these receptors mediate the painful and emetic effects of 5-HT. Selective and potent 5-HT3 receptor antagonists have been shown to block inflammatory and 5-HT induced and potentiated "vascular pain". Based on the hypothesis that 5-HT3 receptor antagonists may block neurogenic dural inflammation in the distribution area of the trigeminal nerve and, thus, could potentially prevent migraine (pain), four highly selective and potent 5-HT3 receptor antagonists have been tested in both the acute and prophylactic treatment of migraine. Unfortunately, except for a clear anti-emetic effect, none of these drugs has shown unequivocal efficacy in the treatment of migraine. This may be partly due to the complex (bell-shaped) dose-response relationship of these compounds, making exact titration of the correct dose difficult. Moreover, most 5-HT3 receptor antagonists have proved to be toxic in man on chronic administration thereby preventing further trials in migraine with adjusted doses. Short-term treatment for cytotoxic drug-induced emesis so far appears to be the only proven indication for 5-HT3 receptor antagonists.
authors.affiliation: Department of Neurology, University Hospital Leiden, The Netherlands.
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
mesh_terms: D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists / Q000627:therapeutic use*
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists