title: Centhaquin antinociception in mice is mediated by α2A- and α2B- but not α2C-adrenoceptors.
abstract: The use of clonidine as a primary and adjuvant analgesic is well-documented. It is known that imidazoline and α2-adrenoceptors are involved in clonidine antinociception. Clonidine also produces antihypertensive actions mediated through the central nervous system. We have reported that centhaquin, a centrally-acting anti-hypertensive drug produces its hypotensive effect through a mechanism of action similar to clonidine. Centhaquin has also been shown to possess significant antinociceptive activity. Centhaquin antinociception is partially blocked by yohimbine, idazoxan, and naloxone; however, the involvement of specific adrenoceptor subtypes (α2A, α2B, or α2C) in centhaquin antinociception is unknown. The present study was conducted to determine antinociceptive properties of centhaquin citrate, a water soluble salt of centhaquin, and involvement of α2A-, α2B-, or α2C-adrenoceptors in centhaquin citrate antinociception in mice. BRL-44408 (α2A-adrenoceptor antagonist), imiloxan (α2B-adrenoceptor antagonist) and JP-1302 (α2C-adrenoceptor antagonist) were used to determine the involvement of α2A-, α2B-, or α2C-adrenoceptors, respectively. Antinociceptive (tail-flick and hot-plate) latencies were determined in male Swiss-Webster mice treated with centhaquin citrate alone and in combination with BRL-44408, imiloxan, or JP-1302. Centhaquin citrate produced significant antinociception in mice (P<0.05) which was unaffected by JP-1302 (P>0.05) but blocked by BRL-44408 (tail-flick test: 49.75% decrease, P<0.05; hot-plate test: 49.12% decrease, P<0.05) and imiloxan (tail-flick test: 46.98% decrease, P<0.05; hot-plate test: 46.42% decrease, P<0.05). This is the first report demonstrating centhaquin citrate antinociception and its blockade by BRL-44408 and imiloxan. We conclude that α2A and α2B but not α2C adrenoceptors are involved in centhaquin antinociception in mice.
authors.affiliation: Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, 555, 31st Street, Downers Grove, IL 60515, United States. SBHALL@midwestern.edu
authors.forename: Shaifali
authors.initials: S
authors.lastname: Bhalla
authors.forename: Izna
authors.initials: I
authors.lastname: Ali
authors.forename: Shridhar V
authors.initials: SV
authors.lastname: Andurkar
authors.forename: Anil
authors.initials: A
authors.lastname: Gulati
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D059225:Nociception / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D010879:Piperazines; D018341:Receptors, Adrenergic, alpha-2; C045913:centhaquine
keywords: Antinociception; BRL-44408; Centhaquin citrate; Imiloxan; JP-1302; α(2A)-, α(2B)-, and α(2C)-adrenoceptors