Sec -Butylpropylacetamide (SPD) has antimigraine properties

Dan Kaufmann, Emily A. Bates, Boris Yagen, Meir Bialer, Gerald H. Saunders, Karen Wilcox, H. Steve White, K. C. Brennan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)924-935
Number of pages12
JournalCephalalgia
Volume36
Issue number10
DOIs
StatePublished - 1 Sep 2016

Bibliographical note

Publisher Copyright:
© 2015 International Headache Society.

Keywords

  • cortical spreading depression
  • mechanical allodynia
  • migraine
  • nitroglycerine test
  • sec -butylpropylacetamide (SPD)

Fingerprint

Dive into the research topics of 'Sec -Butylpropylacetamide (SPD) has antimigraine properties'. Together they form a unique fingerprint.

Cite this