RESUMO
Triptans mediate vasoconstriction of meningeal vessels via stimulation of vascular 5-hydroxytryptamine (5-HT)(1B) receptors. These drugs are recommended for acute treatment in patients with moderate-to-severe migraine attacks and in those patients with mild-to-moderate headache that are not controlled adequately by other agents. Yet, approximately 25% of all migraine users and 40% of all attacks do not respond to triptan treatment. Among the hypothesis to explain this is the possibility that genetic single nucleotide polymorphisms that alter the receptor, for example changing the transcriptional rate and therefore the amount of target protein might change the clinical response to these drugs. In the present contribution, we therefore decided to evaluate whether single nucleotide polymorphisms on the 5-HT(1B) gene might contribute to inter-individual variability in clinical responses to triptans. Two polymorphisms in the promoter region of the 5-HT(1B) receptor (T-261G and A-161T) and the synonymous variation G861C in the coding region were genotyped by restriction fragment length polymorphism in 105 migraine patients. In our sample population, 71% of patients responded to triptans. Allelic and diplotype frequencies were not significantly different between responders and non-responders. On the other hand, extrapolation of in vitro data on promoter activity would suggest that patients with higher copy number of receptors respond slightly better. Our data therefore do not support the involvement of 5-HT(1B) single nucleotide polymorphisms in mediating the inter-individual variability to triptans.
Assuntos
Enxaqueca com Aura/tratamento farmacológico , Enxaqueca sem Aura/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Receptor 5-HT1B de Serotonina/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Triptaminas/farmacologia , Adulto , Idoso , Alelos , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/genética , Enxaqueca sem Aura/genética , Fases de Leitura Aberta , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas , Receptor 5-HT1B de Serotonina/genética , Receptor 5-HT1B de Serotonina/metabolismoRESUMO
Chronic tension type headache (CTTH) has a strong impact on the Quality Of Life (QOL). We carried out an open-label randomized clinical trial on 18 patients with CTTH in order to compare two different regimens of pharmacological prophylaxis: the first provided for the use of amitriptyline 20 mg/d during 3 months, while in the second we combined amitriptyline with tizanidine (4 mg/d) in the first 3 weeks of treatment. Our hypothesis is that the combination therapy may guarantee an improvement of QOL even in the early stages of treatment. In fact, it's as well-known, there is a delay of 2-3 weeks in the prophylactic effect of amitriptyline, with a consequent persistence, in the first phases of therapy, of the headache and its negative impact. We assessed the following outcome measures: frequency, pain intensity, duration of headache and the Headache Impact Test (HIT) score, used as headache-related QOL measure. The combination therapy was effective since the first month of treatment, with a significant reduction of the headache, greater than one obtained with amitriptyline alone, in terms of frequency (-52.3% vs. -40.7%), intensity (-59.51% vs. -20.39%) and duration (-53.17% vs. -36.16%). This trend was confirmed by the HIT. Our data suggest that the combination of tizanidine with amitriptyline is faster than the amitriptyline alone in providing an improvement in the headache pattern and correlated QOL.