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

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概要

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• In the disease states of urinary frequency and urgency, atropine-resistant contractions are known to be involved, in addition to contractions mediated by cholinergic nerves. This study was undertaken to investigate the mechanism underlying the development of atropine-resistant contractions using the representative antimuscarinic drugs solifenacin and tolterodine and also propiverine that has Ca2+ channel–antagonizing activity in addition to antimuscarinic activity. Rat models of urinary frequency were established by intravesical infusion of acetylcholine (ACh) (cholinergic nerve–mediated urinary frequency model), acetic acid (AcOH) [non-adrenergic non-cholinergic nerve (NANC)-mediated urinary frequency model], or CaCl2 (atropine-resistant contractions-mediated urinary frequency model). Cystometrograms were obtained to measure the micturition parameters following oral administration of the aforementioned drugs. Propiverine increased the micturition weight in all the urinary frequency models. Solifenacin and tolterodine increased the micturition weight in the ACh-induced urinary frequency model but neither had any effect in the AcOH- or CaCl2-induced urinary frequency models. While antimuscarinic drugs are, in general, effective for the control of urinary frequency and incontinence, use of drugs possessing inhibitory effects on contractions mediated by cholinergic as well as NANC nerve transmission or Ca2+ influx into smooth muscles is recommended for management of the symptoms in disease states in which atropine-resistant contractions, such as Ca2+- and capsaicin-sensitive sensory nerves, are involved.

• 社団法人 日本薬理学会の論文

著者

• SAKAKIBARA Fukumitsu

  Department of Biotechnology, Faculty of Agriculture, Gifu University

• NANRI Masato

  Department of Pharmacology, Research Institute for Wakan

• Kiniwa Mamoru

  Department of Applied Pharmacology, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., Japan

• Sakakibara Fukumitsu

  Department Of Biotechnology Faculty Of Agriculture Gifu University

• Nanri Masato

  Department Of Pharmacology Taiho Pharmaceutical Co. Ltd.

• Kiniwa Mamoru

  Department Of Applied Pharmacology Tokushima Research Center Taiho Pharmaceutical Co. Ltd.

• Sakakibara Fukumitsu

  Department Of Applied Pharmacology Tokushima Research Center Taiho Pharmaceutical Co. Ltd.

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

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