title: AS1069562, the (+)-isomer of indeloxazine, exerts analgesic effects in rat models of nociceptive pain.
abstract: OBJECTIVE
  The (+)-isomer of indeloxazine AS1069562 has multiple pharmacological actions, such as serotonin (5-HIT) and norepinephrine (NE) reuptake inhibition and analgesic effects in animal models of neuropathic pain. Here, we investigated the analgesic effects of AS1069562 in rat models of inflammatory and noninflammatory nociceptive pain.
  
  
  METHODS
  Adjuvant-induced arthritis (AIA) and bradykinin-induced knee joint pain were used as rat models of inflammatory pain. The chronic phase of monoiodoacetate-induced arthritis (MIA) was used as a rat model of noninflammatory pain. Analgesic effects were evaluated by weight-bearing deficit in the AIA and MIA models and by pain response in the bradykinin-induced knee joint pain model.
  
  
  RESULTS
  In the AIA model and the bradykinin-induced knee joint pain model, AS1069562 significantly ameliorated the pain-related behavior of weight-bearing deficit and the pain response, respectively. AS1069562 also significantly improved the pain-related behavior of weight-bearing deficit in the chronic phase of the MIA model. Further, following monoiodoacetate injection, repeated administration of AS1069562 or duloxetine significantly improved weight-bearing deficit in the MIA model. Interestingly, the analgesic effect of AS1069562 was sustained for 24 hours after the last administration, although the plasma concentration of AS1069562 was reduced to undetectable levels. In contrast, the analgesic effect of duloxetine did not continue after treatment discontinuation.
  
  
  CONCLUSIONS
  AS1069562 exerts analgesic effects on inflammatory and noninflammatory nociceptive pain in rat models of arthritis pain, and repeated administration of AS1069562 exerts a more persistent analgesic effect on arthritis pain than duloxetine. These findings suggest that AS1069562 has an attractive analgesic profile for the treatment of nociceptive pain.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Murai
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takeshita
authors.forename: Fusako
authors.initials: F
authors.lastname: Nishigaki
authors.forename: Megumi
authors.initials: M
authors.lastname: Irie
authors.forename: Seiji
authors.initials: S
authors.lastname: Tamura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Aoki
authors.forename: Nobuya
authors.initials: N
authors.lastname: Matsuoka
mesh_terms: D000700:Analgesics / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D018771:Arthralgia / Q000188:drug therapy* / Q000503:physiopathology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D001920:Bradykinin; D002908:Chronic Disease; D004195:Disease Models, Animal; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology; D005260:Female; D008297:Male; D009025:Morpholines / Q000097:blood / Q000494:pharmacology*; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000700:Analgesics; D009025:Morpholines; C020852:indeloxazine; D000068736:Duloxetine Hydrochloride; D001920:Bradykinin
keywords: AS1069562,; Arthritis,; Duloxetine; Nociceptive pain,; Serotonin and norepinephrine reuptake inhibitor,