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Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

FYO 750

Target

COXs

Action

inhibitors

Mechanism

COX inhibitors(Cyclooxygenases inhibitors)

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Urinary Bladder, Overactive

Originator Organization

Fuji Yakuhin Co., Ltd.

Active Organization-

Inactive Organization

Fuji Yakuhin Co., Ltd.

License Organization-

Drug Highest PhasePendingClinical

First Approval Date-

Regulation-

We previously reported that cyclooxygenase inhibitors improved storage function in rats with detrusor overactivity caused by cerebral infarction via C-fiber suppression but the precise mechanism underlying this effect remained unclear. In this study we investigated the effects of cyclooxygenase inhibitors on stretch evoked adenosine triphosphate and prostaglandin E(2) release from bladder epithelium.

MATERIALS AND METHODS:

Whole bladders excised from normal rats were fixed vertically in an organ bath filled with Krebs solution. Bladders were infused with 0.3 ml Krebs solution (baseline), followed by 0.9 ml vehicle or 1.5 ml vehicle/drug solution, or 0.3 ml protamine sulfate (Wako Pure Chemical Industries, Osaka, Japan), followed by 0.3 ml prostaglandin E(2) (Nacalai Tesque, Kyoto, Japan). Solutions were allowed to stand for 10 minutes and collected. Adenosine triphosphate and prostaglandin E(2) concentrations were measured by luciferin-luciferase assay and enzyme-linked immunoassay, respectively.

RESULTS:

Adenosine triphosphate and prostaglandin E(2) release from bladder epithelium was increased by distention in volume dependent fashion. A 100 μM dose of the nonselective cyclooxygenase inhibitors FYO-750, ketoprofen and indomethacin significantly suppressed the increased adenosine triphosphate and prostaglandin E(2) release. Inhibition of adenosine triphosphate release by 100 μM FYO-750 and indomethacin was antagonized by prostaglandin E(2) co-injection. Prostaglandin E(2) increased adenosine triphosphate release in a nondistending condition, and the 1 μM of the selective EP1 and EP3 receptor antagonists ONO-8711 and ONO-AE5-599, respectively, significantly suppressed the increased adenosine triphosphate release.

CONCLUSIONS:

Results indicate that cyclooxygenase inhibitors suppress adenosine triphosphate release from bladder epithelium via decreasing prostaglandin E(2). EP1 and/or EP3 receptors appear to participate in this effect.

01 Feb 2010·The Journal of urologyQ1 · MEDICINE

Improvement in Neurogenic Detrusor Overactivity by Peripheral C Fiber's Suppression With Cyclooxygenase Inhibitors

Q1 · MEDICINE

Article

Author: Yokoyama, Osamu ; Tanaka, Ippei ; Akino, Hironobu ; Nagase, Keiko ; Aoki, Yoshitaka ; Tanase, Kazuya

PURPOSE:

Cyclooxygenase inhibitors decrease micturition frequency in animals with bladder inflammation but to our knowledge the influence of cyclooxygenase inhibitors on detrusor overactivity has not been investigated. We evaluated the effects, and the site and mechanism of action of cyclooxygenase inhibitors on detrusor overactivity induced by cerebral infarction.

MATERIALS AND METHODS:

Cerebral infarcted rats underwent cumulative intravenous administration of the selective cyclooxygenase-1 inhibitor SC-560 (Sigma), the selective cyclooxygenase-2 inhibitor rofecoxib (Kemprotec, Middlesbrough, United Kingdom) or the nonselective cyclooxygenase inhibitor FYO-750 hourly plus a single intravenous administration of SC-560, rofecoxib or SC-560 plus rofecoxib. To evaluate the site of action cerebral infarcted rats underwent single intracerebroventricular or intrathecal administration of FYO-750. To evaluate the mechanism of action FYO-750 was intravenously administered in diuretic rats or cerebral infarcted rats pretreated with resiniferatoxin.

RESULTS:

For cumulative administration SC-560 (0.3 mg/kg), rofecoxib (0.3 mg/kg) and FYO-750 (0.1 to 1 mg/kg) significantly increased bladder capacity. For single administration neither SC-560 (0.03 mg/kg) nor rofecoxib (0.03 mg/kg) affected bladder capacity but SC-560 plus rofecoxib significantly increased bladder capacity vs vehicle. Intracerebroventricular and intrathecal administration of FYO-750 did not affect bladder capacity. FYO-750 did not affect urinary production in diuretic rats and the effects of FYO-750 were blocked by resiniferatoxin except at the highest drug dose.

CONCLUSIONS:

Results indicate that cyclooxygenase inhibitors improve detrusor overactivity caused by cerebral infarction by suppressing peripheral C fiber's without affecting urinary production. The nonselective cyclooxygenase inhibitor showed more potent efficiency than the selective cyclooxygenase-1 or the cyclooxygenase-2 inhibitor alone.

100 Deals associated with FYO-750

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