title: sec-Butylpropylacetamide (SPD), a new amide derivative of valproic acid for the treatment of neuropathic and inflammatory pain.
abstract: Chronic pain is a multifactorial disease comprised of both inflammatory and neuropathic components that affect ∼20% of the world's population. sec-Butylpropylacetamide (SPD) is a novel amide analogue of valproic acid (VPA) previously shown to possess a broad spectrum of anticonvulsant activity. In this study, we defined the pharmacokinetic parameters of SPD in rat and mouse, and then evaluated its antinociceptive potential in neuropathic and acute inflammatory pain models. In the sciatic nerve ligation (SNL) model of neuropathic pain, SPD was equipotent to gabapentin and more potent than its parent compound VPA. SPD also showed either higher or equal potency to VPA in the formalin, carrageenan, and writhing tests of inflammatory pain. SPD showed no effects on compound action potential properties in a sciatic nerve preparation, suggesting that its mechanism of action is distinct from local anesthetics and membrane stabilizing drugs. SPD's activity in both neuropathic and inflammatory pain warrants its development as a potential broad-spectrum anti-nociceptive drug.
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Kaufmann
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: West
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Misty D
authors.initials: MD
authors.lastname: Smith
authors.affiliation: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; David R. Bloom Center for Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Yagen
authors.affiliation: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; David R. Bloom Center for Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Meir
authors.initials: M
authors.lastname: Bialer
authors.affiliation: Department of Cell and Animal Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Marshall
authors.initials: M
authors.lastname: Devor
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA. Electronic address: hswhite@uw.edu.
authors.forename: H Steve
authors.initials: HS
authors.lastname: White
authors.affiliation: Department of Neurology, University of Utah, Salt Lake City, UT, USA. Electronic address: K.C.Brennan@hsc.utah.edu.
authors.forename: K C
authors.initials: KC
authors.lastname: Brennan
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D000077206:Gabapentin; D007249:Inflammation / Q000150:complications; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000577:Amides; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; C570212:sec-butyl-propylacetamide; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000077206:Gabapentin
keywords: Carrageenan test; Chung model; Compound action potentials; Formalin test; Pharmacokinetics; Writhing test; sec-Butylpropylacetamide (SPD)