학술논문

sec-Butylpropylacetamide (SPD) has antimigraine properties.
Document Type
Article
Source
Cephalalgia. Sep2016, Vol. 36 Issue 10, p924-935. 12p. 1 Diagram, 5 Graphs.
Subject
*HEADACHE treatment
*MIGRAINE
*MIGRAINE prevention
*VALPROIC acid
*SPREADING cortical depression
*NEURONS
THERAPEUTIC use of nitroglycerin
Language
ISSN
0333-1024
Abstract
Background: Though migraine is disabling and affects 12%-15% of the population, there are few drugs that have been developed specifically for migraine prevention. Valproic acid (VPA) is a broad-spectrum antiepileptic drug (AED) that is also used for migraine prophylaxis, but its clinical use is limited by its side effect profile. sec-Butylpropylacetamide (SPD) is a novel VPA derivative, designed to be more potent and tolerable than VPA, that has shown efficacy in animal seizure and pain models. Methods: We evaluated SPD's antimigraine potential in the cortical spreading depression (CSD) and nitroglycerin (NTG) models of migraine. To evaluate SPD's mechanism of action, we performed whole-cell recordings on cultured cortical neurons and neuroblastoma cells. Results: In the CSD model, the SPD-treated group showed a significantly lower median number of CSDs compared to controls. In the NTG-induced mechanical allodynia model, SPD dose-dependently reduced mechanical sensitivity compared to controls. SPD showed both a significant potentiation of GABA-mediated currents and a smaller but significant decrease in NMDA currents in cultured cortical neurons. Kainic acid-evoked currents and voltage-dependent sodium channel currents were not changed by SPD. Conclusions: These results demonstrate SPD's potential as a promising novel antimigraine compound, and suggest a GABAergic mechanism of action. [ABSTRACT FROM AUTHOR]