Thus, acute migraine attacks can effectively be treated with triptans, highly selective 5-H1B/1D receptor agonists, which act mainly via vasoconstriction of dilated cerebral blood vessels, inhibition of the release of neuropeptides such as substance P, and inhibition of nociceptive neurotransmission. Typical antidepressants, Inhibitors,research,lifescience,medical eg, amitriptyline or fluoxetine,
are also effective in the preventive treatment of migraine, probably via their influence on the neurotransmitter systems. These findings are a hint for possible common pathophysiological mechanisms for migraine and depression, and lead to the question of whether polymorphisms relevant for affective disorders might also be involved
in migraine. Genes of the serotonergic system Among the most frequently investigated candidate genes of the serotonergic pathway is the serotonin transporter (5-HTT), which cleaves the synaptic cleft from neurotransmitters and thus limits the duration of Inhibitors,research,lifescience,medical 5-HT function. Two selleck kinase inhibitor polymorphic sites within the 5-HTT gene are partieularly interesting: one located in the promoter region with a deletion/insertion variation of 44 bp, creating short (S) and long (L) alleles, the 5-HTT-linked promoter region (HTTLPR); and a variable number of tandem repeats (VNTR) polymorphism, located Inhibitors,research,lifescience,medical in the second intron of the gene.18 The presence of the S allele of Inhibitors,research,lifescience,medical the HTTLPR is associated with decreased 5-HT reuptake, which, in turn, results in a longer duration of the serotonergic activity.19
Although the results with psychiatric patients are not conelusive, the polymorphism may be of some importance in anxiety-related personality traits,20 depression,21 and sulcidality 22 However, for migraine sufferers, no association has been found to date for this genetic variant of the 5-HTT.23,24 In contrast, the VNTR polymorphism, whose functional significance remains to Inhibitors,research,lifescience,medical be elucidated, seems to play a role in migraine, as the frequency of the ST12.10 allele was increased.23,24 Moreover, differences were observed between migraine with and without aura, thus being in concordance Cilengitide with the assumption that these forms of the disorder might be etiologically distinct.24 These data support the view that susceptibility to migraine has a genetic component, which may, in some cases, be associated with a locus at or near 5-HTT. Further studies investigated genetic variations in the 5-HT http://www.selleckchem.com/products/Paclitaxel(Taxol).html receptors. Whereas no association was observed for the 5-HT2c subtype,25 a polymorphism in the 5-HT2A receptor gene (a T to C transition at position 102), which has been repeatedly associated with psychiatric disorders and treatment response,26,27 also seems to be relevant in migraine.