Biol. Pharm. Bull. 29(7) 1397—1400 (2006)

nence Society (ICS) as symptoms of urgency with or without urge incontinence, usually with increased frequency and nocturia. Since both normal voiding processes and involuntary detrusor contractions during bladder filling are mediated by muscarinic receptors, anticholinergic agents, such as oxybutynin, are currently recommended as first-line therapy for the treatment of overactive bladder. Although the efficacy of these agents has been demonstrated, their side effects cause problems in geriatric patients. Especially, the dry mouth caused by oral oxybutynin, a more potent inhibitor of cholinergic salivation than bladder contraction, often leads to the discontinuation of treatment. Bladder-selective anticholinergic agents such as solifenacin and tolterodine which may reduce or even eliminate these problems are now under development. In particular contrast to oxybutynin, the attenuation of cholinergic responses by solifenacin has been shown to be less potent in salivary gland than in bladder detrusor muscle. However, the mechanism underlying solifenacin’s relatively weak inhibition of salivary secretion has not been clarified. The therapeutic and unwanted effects of anticholinergic agents in patients with overactive bladder stem from the blockade of muscarinic receptors in the bladder and non-target tissues, respectively. Muscarinic receptors have been classified into five subtypes (M1—M5), based on genetic and/or pharmacological properties. The M3 subtype is preferentially distributed in the salivary gland, and has been shown using M3 receptor knockout mice to play a key role in salivary secretion. Oxybutynin and solifenacin have shown high affinity for this subtype in in vitro binding assays with human muscarinic receptor subtypes expressed in Chinese hamster ovary cells. The present study was therefore conducted to characterize the suppression of cholinergic salivation and exocrine muscarinic receptor binding in mice receiving oral administration of solifenacin or oxybutynin. MATERIALS AND METHODS