Sustained pain relief with dihydroergotamine in migraine is potentially due to persistent binding to 5-HT1B and 5-HT1D receptors

摘要: Several studies show that dihydroergotamine (DHE) produces sustained migraine pain relief, measured up to 48 hours, although its serum half-life is only 10-13 hours. The extended duration of action has been attributed an active metabolite (8’-OH-DHE) with a much longer than the parent compound. However, recent pharmacokinetic demonstrate DHE metabolites in humans are too low have substantial clinical effect and probably do not contribute efficacy. We hypothesized long-lasting most likely due prolonged binding receptors, rather half-life. Therefore, investigate mechanism relief observed DHE, we compared serotonin receptors vs. sumatriptan. Duration receptor expressed as dissociation constant (koff) receptor-ligand complex, using competitive radioligand assay. sumatriptan were tested human 5-HT1B 5-HT1D this study. halflife on approximately 10 times (5-HT1B: 1.38 h for 0.17 sumatriptan; 5HT1D: 1.28 0.09 sumatriptan). binds 8-14 does These play key role acute treatment and, therefore, these may be seen during migraine. Acknowledgements Study supported by MAP Pharmaceuticals, Inc. was conducted EuroScreen S.A. (Belgium).