title: sec-Butylpropylacetamide (SPD) has antimigraine properties.
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.
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, USA Department of Neurology, University of Utah, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Kaufmann
authors.affiliation: Department of Pediatrics, University of Colorado Denver School of Medicine, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Bates
authors.affiliation: Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Israel David R. Bloom Center for Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Yagen
authors.affiliation: Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Israel David R. Bloom Center for Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
authors.forename: Meir
authors.initials: M
authors.lastname: Bialer
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, USA.
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Saunders
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Wilcox
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, USA.
authors.forename: H Steve
authors.initials: HS
authors.lastname: White
authors.affiliation: Department of Neurology, University of Utah, USA K.C.Brennan@hsc.utah.edu.
authors.forename: K C
authors.initials: KC
authors.lastname: Brennan
mesh_terms: D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008881:Migraine Disorders / Q000503:physiopathology* / Q000517:prevention & control*; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000577:Amides; D000927:Anticonvulsants; C570212:sec-butyl-propylacetamide; D014635:Valproic Acid
keywords: cortical spreading depression; mechanical allodynia; migraine; nitroglycerine test; sec-butylpropylacetamide (SPD)