title: Assessment of the analgesic effect of centhaquin in mouse tail flick and hot-plate tests.
abstract: BACKGROUND
  Centhaquin is a centrally acting hypotensive drug like clonidine. Clonidine also produces analgesia and hypothermia in mice and potentiates morphine analgesia. Clonidine analgesia is blocked by idazoxan and naloxone while it is potentiated by BQ123 and sulfisoxazole. This study was conducted to determine the analgesic and hypothermic properties of centhaquin, and to assess whether it potentiates morphine analgesia. Yohimbine (α(2)-adrenergic antagonist), idazoxan (imidazoline/α(2)-adrenergic antagonist), naloxone (opioid antagonist), and BQ123 and sulfisoxazole (endothelin ET(A) antagonists) were used to study the involvement of these receptors in centhaquin analgesia and hypothermia.
  
  
  METHODS
  Analgesic (tail flick and hot-plate tests) latencies and body temperatures were measured in male Swiss Webster mice treated with vehicle plus centhaquin, antagonists plus centhaquin or centhaquin plus morphine.
  
  
  RESULTS
  Centhaquin produced dose-dependent analgesia which was partially blocked by yohimbine, idazoxan and naloxone. BQ123 and sulfisoxazole did not affect centhaquin analgesia. Morphine analgesia was not potentiated by centhaquin. Centhaquin produced mild hypothermia which was not blocked by yohimbine, idazoxan, naloxone, BQ123 or sulfisoxazole.
  
  
  CONCLUSIONS
  This is the first report demonstrating the analgesic activity of centhaquin. The α(2)-adrenergic, imidazoline and opioid receptors are involved in mediating centhaquin analgesia. Endothelin ET(A) receptors do not play a role in centhaquin analgesia; centhaquin does not augment morphine analgesia.
authors: Department of Pharmaceutical Sciences, Midwestern University Chicago College of Pharmacy, Downers Grove, Ill. 60515, USA. sandur@midwestern.edu
authors: Shridhar V
authors: SV
authors: Andurkar
authors: Anil
authors: A
authors: Gulati
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001831:Body Temperature / Q000187:drug effects; D004347:Drug Interactions; D065130:Endothelin A Receptor Antagonists; D006358:Hot Temperature; D019329:Idazoxan / Q000627:therapeutic use; D054755:Imidazoline Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000627:therapeutic use; D009270:Naloxone / Q000627:therapeutic use; D009292:Narcotic Antagonists; D010146:Pain / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D044022:Receptor, Endothelin A / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D015016:Yohimbine / Q000627:therapeutic use
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D000701:Analgesics, Opioid; D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D054755:Imidazoline Receptors; D009292:Narcotic Antagonists; D010879:Piperazines; D044022:Receptor, Endothelin A; D018341:Receptors, Adrenergic, alpha-2; D011957:Receptors, Opioid; D015016:Yohimbine; D009270:Naloxone; C045913:centhaquine; D009020:Morphine; D019329:Idazoxan