sec-Butylpropylacetamide (SPD), a new amide derivative of valproic acid for the treatment of neuropathic and inflammatory pain

Pharmacol Res. 2017 Mar;117:129-139. doi: 10.1016/j.phrs.2016.11.030. Epub 2016 Nov 24.

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.

Keywords: Carrageenan test; Chung model; Compound action potentials; Formalin test; Pharmacokinetics; Writhing test; sec-Butylpropylacetamide (SPD).

MeSH terms

  • Amides / pharmacology*
  • Amines / pharmacology
  • Analgesics / pharmacology
  • Animals
  • Cyclohexanecarboxylic Acids / pharmacology
  • Disease Models, Animal
  • Gabapentin
  • Inflammation / complications
  • Male
  • Mice
  • Neuralgia / drug therapy*
  • Pain / drug therapy*
  • Pain / etiology
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / drug effects
  • Valproic Acid / analogs & derivatives*
  • Valproic Acid / pharmacology*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Amides
  • Amines
  • Analgesics
  • Cyclohexanecarboxylic Acids
  • sec-butyl-propylacetamide
  • gamma-Aminobutyric Acid
  • Valproic Acid
  • Gabapentin