Department of Pathophysiology, Jagiellonian University, Medical College, Cracow, Poland.
Introduction: Overactive bladder (OAB) is a common disease entity with complex pathogenesis that involves neurogenic, myogenic and abnormal paracrine urothelial activity mechanisms. Our objective was to estimate bladder functioning in urodynamic studies in experimental, both acute (AOAB) and chronic (COAB) cyclophosphamide (CYP)-evoked OAB model in response to melatonin (MLT; antioxidant and MT receptor agonist) or agomelatine (AMT; MT receptor agonist and 5HT2C receptor antagonist).
Material/Methods: Seven groups were studied: 1 - control, 2-4 - MLT treated AOAB and COAB rats, 5-7 - AMT treated AOAB and COAB rats. AOAB model was evoked by single CYP administration (IP 200 mg/kg body weight), while COAB one was induced by a four-time administration of CYP (IP 75 mg/kg body weight). Each group underwent urethane anesthesia to perform urodynamic recordings in resting conditions and after administration 50 (group 2 or 5), 75 (group 3 or 6) or 100 mg/kg (group 4 or 7) of melatonin (groups 2-4) or agomelatine (groups 5-7), followed by classical urodynamic parameters assessment.
Results: Neither melatonin nor agomelatine did not affect urodynamic parameters in the AOAB rats. In COAB model, after 75 and 100 mg/kg of MLT we revealed an improvement in urodynamic parameters. AMT (75 and 100 mg/kg) administration caused deterioration of urodynamic findings suggesting bladder overactivity exacerbation.
Disscussion: In summary, melatonin ameliorates bladder overactivity in cyclophosphamide-induced COAB. Agomelatine, contrary to melatonin, aggravates bladder dysfunction in this group. These findings suggest that the improvement in urodynamic parameters after melatonin administration may be due to its antioxidative profile and is not related to MT receptors activation. However, agomelatine's unfavorable action on the bladder, resulting in its overactivity in COAB group, may not only be the result of MT receptor activation without the concomitant antioxidative effects but may also occur secondarily to co-existing 5HT2C receptor antagonism.
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Reference: Postepy Hig Med Dosw (Online). 2011 Nov 23;65:725-33.