The Involvement of l-Arginine-Nitric Oxide-cGMP-ATP-Sensitive K+ Channel Pathway in Antinociception of BBHC, a Novel Diarylpentanoid Analogue, in Mice Model

Molecules. 2021 Dec 8;26(24):7431. doi: 10.3390/molecules26247431.

Abstract

The present study focuses on the possible involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway in the antinociceptive activity of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC) via a chemical nociceptive model in mice. The antinociceptive action of BBHC (1 mg/kg, i.p.) was attenuated by the intraperitoneal pre-treatment of l-arginine (a nitric oxide synthase precursor) and glibenclamide (an ATP-sensitive K+ channel blocker) in acetic acid-induced abdominal constriction tests. Interestingly, BBHC's antinociception was significantly enhanced by the i.p. pre-treatment of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase (p < 0.05). Altogether, these findings suggest that the systemic administration of BBHC is able to establish a significant antinociceptive effect in a mice model of chemically induced pain. BBHC's antinociception is shown to be mediated by the involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway, without any potential sedative or muscle relaxant concerns.

Keywords: ATP-sensitive potassium channel; BBHC; antinociceptive; cGMP; diarylpentanoid; nitric oxide.

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Animals
  • Arginine / metabolism
  • Cyclic GMP / metabolism
  • KATP Channels / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide / metabolism
  • Pain* / chemically induced
  • Pain* / drug therapy
  • Pain* / metabolism

Substances

  • Analgesics
  • KATP Channels
  • Nitric Oxide
  • Arginine
  • Cyclic GMP