The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Bladder Selectivity Based on In Vivo Drug–Receptor Binding Characteristics of Antimuscarinic Agents for Treatment of Overactive Bladder
| Autor: | Shuji Maruyama, Shizuo Yamada, Akira Yoshida, Tomomi Fujino, Yuko Taki, Yoshihiko Ito |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Urinary Bladder Muscarinic Antagonists Pharmacology Mice Drug Delivery Systems Internal medicine Muscarinic Receptor Binding medicine Darifenacin Animals Humans Radionuclide Imaging Oxybutynin Solifenacin Antimuscarinic Agent Urinary Bladder Overactive Chemistry lcsh:RM1-950 Brain medicine.disease Macaca mulatta Receptors Muscarinic Rats lcsh:Therapeutics. Pharmacology Endocrinology Overactive bladder Autoradiography Molecular Medicine Propiverine Tolterodine Protein Binding medicine.drug |
| Zdroj: | Journal of Pharmacological Sciences, Vol 112, Iss 2, Pp 142-150 (2010) |
| ISSN: | 1347-8648 1347-8613 |
| DOI: | 10.1254/jphs.09r14fm |
| Popis: | We have reviewed the binding of antimuscarinic agents, used to treat urinary dysfunction in patients with overactive bladder, to muscarinic receptors in target and non-target tissues in vivo. Transdermal administration of oxybutynin in rats led to significant binding in the bladder without long-term binding in the submaxillary gland and the abolishment of salivation evoked by oral oxybutynin. Oral solifenacin showed significant and long-lasting binding to muscarinic receptors in mouse tissues expressing the M3 subtype. Oral tolterodine bound more selectively to muscarinic receptors in the bladder than in the submaxillary gland in mice. The muscarinic receptor binding activity of oral darifenacin in mice was shown to be pronounced and long-lasting in the bladder, submaxillary gland, and lung. In vivo quantitative autoradiography using (+)N-[11C] methyl-3-piperidyl benzilate in rats showed significant occupancy of brain muscarinic receptors on intravenous injection of oxybutynin, propiverine, solifenacin, and tolterodine. The estimated in vivo bladder selectivity compared to brain was significantly greater for solifenacin and tolterodine than oxybutynin. Darifenacin occupied few brain muscarinic receptors. Similar findings were also observed with positron emission tomography in conscious rhesus monkeys. The newer generation of antimuscarinic agents may be advantageous in the bladder selectivity after systemic administration. Keywords:: overactive bladder, antimuscarinic, in vivo receptor binding, bladder, other tissue, lower urinary tract |
| Databáze: | OpenAIRE |
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