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

Abstract

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 approximately 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 < 0.05) dose-dependent increase in NVCs and a decrease in ICI. Rats pre-treated with MN-001 at 30 and 50 mg/kg (groups 4 and 5) had significantly fewer NVCs and a greater ICI than rats in group 2 (P < 0.05).

CONCLUSION:

OA challenge in OA-sensitized rats produces bladder hyperactivity, as reflected in significantly more NVCs and a lower ICI. At doses of 30 and 50 mg/kg orally, MN-001 produces significant protection against the OA-induced bladder hyperactivity. MN-001 might have a role in managing mast cell activity and the associated bladder symptoms in patients with interstitial cystitis.

• Authors: Mahadevan Rajasekaran, Kenneth W Locke, C Lowell Parsons
• Journal: BJU international (BJU Int) Vol. 98 Issue 2 Pg. 430-4 (Aug 2006) ISSN: 1464-4096 [Print] England
• PMID: 16879690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents

Topics

• Administration, Intravesical
• Administration, Oral
• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Female
• Male
• Mast Cells
• Muscle Contraction (drug effects)
• Rats
• Rats, Sprague-Dawley
• Urinary Incontinence (drug therapy, pathology, physiopathology)
• Urodynamics