title: Effects of IP-751, ajulemic acid, on bladder overactivity induced by bladder irritation in rats.
abstract: OBJECTIVE
  Ajulemic acid (IP-751) is a synthetic analog of tetrahydrocannabinol, which is a major ingredient of the plant Cannabis. IP-751 reportedly shows potent anti-inflammatory activity and is a powerful analgesic agent. Thus, we examined whether IP-751 can suppress urinary frequency induced by nociceptive stimuli in the bladder.
  
  
  METHODS
  Continuous cystometry (infusion rate 0.04 mL/min) under urethane anesthesia was performed to evaluate the effect of intravenous injection of IP-751 with or without a cannabinoid-1 receptor antagonist (AM251) or a cannabinoid-2 receptor antagonist (AM630) on bladder function in normal rats and rats with urinary frequency induced by intravesical infusion with 0.25% acetic acid or cyclophosphamide (CYP) (150 mg/kg intraperitoneally, 48 hours before cystometrography).
  
  
  RESULTS
  When 10 mg/kg of IP-751 was injected in normal rats, the intercontraction interval (ICI) and pressure threshold increased. A 0.25% acetic acid infusion induced urinary frequency, as evidenced by a reduction in ICIs, which were suppressed by injection of IP-751 (10 mg/kg). Urinary frequency, indicated by significant ICI reductions, was also observed in the CYP-treated rats. Administration of IP-751 (10 mg/kg) significantly suppressed CYP-induced urinary frequency, as evidenced by the increase in the ICI. When AM251, but not AM630, was administered before IP-751, the IP-751-induced increases in the ICI and pressure threshold were prevented in all three groups. In addition, administration of AM251 alone decreased the ICIs in CYP-treated rats.
  
  
  CONCLUSIONS
  IP-751 can suppress normal bladder activity and urinary frequency induced by bladder nociceptive stimuli, probably by suppression of bladder afferent activity. These inhibitory effects of IP-751 are at least in part mediated by the cannabinoid-1 receptor.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Shiro
authors.initials: S
authors.lastname: Hiragata
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Ogawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Seki
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishizawa
authors.forename: Fernando
authors.initials: F
authors.lastname: de Miguel
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology
chemical_list: D007375:Interleukin-1; D013759:Dronabinol; C471849:lenabasum