DEMONSTRATION OF BLADDER SELECTIVE MUSCARINIC RECEPTOR BINDING BY INTRAVESICAL OXYBUTYNIN TO TREAT OVERACTIVE BLADDER
| Autor: | Ryohei Kimura, Tomomi Oki, Shizuo Yamada, Motoaki Saito, Ikuo Miyagawa |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Urology Urinary Bladder Rats Sprague-Dawley Oral administration Internal medicine Muscarinic acetylcholine receptor Muscarinic Receptor Binding Animals Medicine Oxybutynin Urinary bladder business.industry Urinary Bladder Diseases medicine.disease Receptors Muscarinic Rats Administration Intravesical Endocrinology medicine.anatomical_structure Overactive bladder Pilocarpine Mandelic Acids business Urinary bladder disease medicine.drug |
| Zdroj: | Journal of Urology. 172:2059-2064 |
| ISSN: | 1527-3792 0022-5347 |
| DOI: | 10.1097/01.ju.0000138472.16876.8d |
| Popis: | The current study was done to elucidate the in vivo mechanism of action of intravesical instillation of oxybutynin to treat overactive bladder.In rats receiving oral and intravesical oxybutynin we measured muscarinic receptors in the bladder and other tissues by radioligand binding assay using [3H]NMS ([N-methyl-3H] scopolamine methyl chloride) with the simultaneous measurement of plasma concentrations of oxybutynin and its active metabolite N-desethyl-oxybutynin. Pilocarpine induced salivary secretion was also measured.Following oral administration of oxybutynin there was a significant increase in the apparent dissociation constant (Kd) for specific [3H]NMS binding in the bladder, submaxillary gland, heart and colon of rats at 1 and 3 hours with a consistent decrease in the maximal number of binding sites (Bmax) in the submaxillary gland. Furthermore, a marked and prolonged decrease in pilocarpine induced salivary secretion in rats was observed by oral oxybutynin. In contrast, intravesical instillation of oxybutynin produced a significant increase in Kd for specific [3H]NMS binding in the bladder of rats at 0.5 to 4 hours later and also in the submaxillary gland only at 0.5 hours later. The enhancement in Kd was much larger and longer lasting in the bladder than in the submaxillary gland. Moreover, intravesical oxybutynin had little muscarinic receptor binding activity in the heart and colon, and little significant suppression of pilocarpine induced salivation in rats. The plasma concentrations of oxybutynin and N-desethyl-oxybutynin were much higher in rats receiving oxybutynin orally than intravesically.Intravesical oxybutynin in rats may cause selective binding of bladder muscarinic receptors via a direct local effect, while oral oxybutynin may exert predominant binding of salivary gland receptors. |
| Databáze: | OpenAIRE |
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