Migraine is a common type of headache and its most severe attacks are usually treated with triptans, the efficacy of which is extremely variable. Several SNPs in genes involved in metabolism and target mechanisms of triptans have been described. To define an association between genetic profile and triptan response, we classified a migrainous population on the basis of triptan response and characterized it for polymorphisms in the genes coding for monoamine oxidase A, G protein β3 and the cytochrome CYP1A2. Analysis of the association between genotypic and allelic frequencies of the analyzed SNPs and the grade of response to triptan administration showed a significant correlation for MAOA uVNTR polymorphism. Further stratification of patients in abuser and non-abuser groups revealed a significant association with triptan overuse and, within the abusers, with drug response to the CYP1A2*1F variant.
Pharmacogenomic studies of triptans suggest that some genetic determinants influence drug response, but the complexity of the field calls for application of a systematic approach to genetic association studies, allowing identification of a therapy response prediction panel with adequate predictive power.
Frovatriptan has been developed in order to improve safety and efficacy of triptans. It shows a favorable tolerability and efficacy profile, limited to 24/48-h headache recurrence, when compared with other triptans. Preclinical data suggest that the pharmacokinetic profile of frovatriptan may differ from other available triptans. In fact, among triptans, frovatriptan showed the highest potency at the 5-HT1B receptor (8.2) and the longer half-life (26 h). These parameters determine the clinical properties of frovatriptan; in particular the lowest rate of headache recurrence in comparison with other triptans.
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