MN‐001, a novel oral anti‐inflammatory agent, suppresses bladder hyperactivity in a rat model

• Published in: BJU international 2006-08, Vol.98 (2), p.430-434
• Main Authors: RAJASEKARAN, MAHADEVAN, LOCKE, KENNETH W., PARSONS, C. LOWELL
• Format: Article
• Language: English
• Subjects: Administration, Intravesical; Administration, Oral; Animals; Anti-Inflammatory Agents - administration & dosage; anti‐inflammatory agent; Biological and medical sciences; bladder; drug effects; Female; interstitial cystitis; Male; Mast Cells; Medical sciences; Muscle Contraction - drug effects; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Urinary Incontinence - drug therapy; Urinary Incontinence - pathology; Urinary Incontinence - physiopathology; Urinary system; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Urodynamics
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2006.06274.x

OBJECTIVE To evaluate the effects of MN‐001, a novel orally active anti‐inflammatory agent, in suppressing the bladder hyperactivity resulting from ovalbumin (OA)‐induced mast‐cell stimulation in a rat model. MATERIALS AND METHODS Sprague‐Dawley rats of both sexes were divided into five groups of 10 each, with group 1 as the control and groups 2–5 undergoing OA sensitization to produce mast‐cell degranulation using an established method. At 14 days after sensitization, rats were given an acute intravesical challenge: in group 1, by saline (control), and in groups 2–5, with ≈ 2 mL of OA (10 mg/mL in sterile saline). Groups 3–5 received the investigational agent MN‐001 orally at 10, 30 or 50 mg/kg, respectively, 1 h before intravesical OA challenge. Urodynamics were then evaluated to quantify the frequency of contractions (voids), intercontractile interval (ICI) and non‐voiding contractions (NVCs). RESULTS Acute intravesical OA challenge in rats in group 2 caused contractions of bladder smooth muscle, leading to a significant (P