The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

Abstract

Abstract. Overactive bladder (OAB) syndrome is a common condition that is most often observed in the elderly. Pharmacological treatment with muscarinic receptor antagonists has been most widely used for OAB. An antimuscarinic agent, solifenacin, showed the highest affinity for the muscarinic M 3 receptor, which mediates urinary bladder contraction. In preclinical studies, solifenacin exhibited a highly bladder-selective profile compared with other antimuscarinic agents. Solifenacin was also shown to increase bladder capacity without affecting residual urine in an OAB model of rats. Urgency is now considered to result from overactivation of afferent nerves from the urinary bladder. It has been reported that afferent nerves are located adjacent to the urothelium, and stimulation of muscarinic receptors expressed on the urothelium may contribute to the activation of afferent nerves via non-neuronal ATP release. Solifenacin produces its inhibitory effect on bladder afferent activity partly via the suppression of non-neuronal ATP release. Clinically, solifenacin ameliorates all symptoms in OAB patients; and in particular, it produces a significant decrease in urgency episodes, which is the principal symptom of OAB. The pharmacological profile of solifenacin is therefore considered to contribute to its beneficial effects of high efficacy against OAB symptoms with good tolerability.

Are Antimuscarinic Drugs Effective Against Urinary Frequency Mediated by Atropine-Resistant Contractions?

“…It was thus inferred that in addition to the antimuscarinic activity, the Ca 2+ channel-antagonizing activity might also contribute to the control of ACh-induced urinary frequency. In the ACh-induced urinary frequency model, the antimuscarinic agents used in this study were demonstrated to cause a dose-dependent increase in the micturition weight; this finding was consistent with previously reported data obtained in a rat model of cerebral infarction (16).…”

Quantitation of Solifenacin in Human Plasma using a Specific and Sensitive Liquid Chromatography-Tandem Mass Spectrometry Technique

“…Solifenacin succinate is a competitive muscarinic receptor antagonist that blocks specifically M3 receptors on the urinary bladder, and thus is indicated to manage the OAB syndrome in adults [2]. The validation process has shown that our assay was specific, accurate, precise and reproducible.…”

“…The sudden involuntary contraction of the urinary bladder, caused by the pathophysiological mechanisms of the OAB syndrome, results in the clinical presentation of urgency, frequency and nocturia that may or may not be accompanied with incontinence [2]. The activation of the parasympathetic nervous system, and thus the muscarinic receptors on the smooth muscles of the bladder, mediates these annoying symptoms of the OAB syndrome [3].…”

Insight into New Potential Targets for the Treatment of Overactive Bladder and Detrusor Overactivity

“…A significant increase in M2R and M3R immunoreactivity in myofibroblasts-like cells was found in bladder specimens from patients with idiopathic DO (IDO) as compared with that in controls, furthermore showing a significant correlation with the urgency score [13]. It has been also reported that afferent nerves are located adjacent to the urothelium, and stimulation of MRs expressed on the urothelium may contribute to the activation of afferent nerves via non-neuronal ATP release, thus reducing urgency [14]. Activation of MRs in the urothelium releases substances that modulate afferent nerves [15].…”