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MN‐001, a novel oral anti‐inflammatory agent, suppresses bladder hyperactivity in a rat model
Author(s) -
RAJASEKARAN MAHADEVAN,
LOCKE KENNETH W.,
PARSONS C. LOWELL
Publication year - 2006
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2006.06274.x
Subject(s) - medicine , sensitization , degranulation , saline , urinary bladder , stimulation , ovalbumin , urology , pharmacology , immunology , receptor , immune system
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 < 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.