| Effects of KMD-3213, a uroselective alpha 1A-adrenoceptor antagonist, on the tilt-induced blood pressure response in normotensive rats. | |
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MedLine Citation:
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PMID: 12419883 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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KMD-3213 ((-)-1-(3-hydroxypropyl)-5-((2R)-2-[[2-([2-[(2,2,2-trifluoroethyl)oxy]phenyl]oxy)ethyl]amino]propyl)-2,3-dihydro-1H-indole-7-carboxamide), an alpha(1A)-adrenoceptor antagonist with potency similar to that of tamsulosin, is under development for the treatment of bladder outlet obstruction in patients with benign prostatic hypertrophy. In the present study, we investigated the effects of KMD-3213 on the tilt-induced blood pressure response in anesthetized normotensive rats. Male normotensive Sprague-Dawley rats were placed in the supine position on a board under cocktail anesthetization (alpha-chloralose, urethane and sodium pentobarbital). The arterial blood pressure was measured from the carotid artery. The animals were given consistent 45 degrees head-up tilt from the horizontal position, following the transient decrease in the blood pressure, and then recovery of the blood pressure to the normal level. Significant orthostatic hypotension was seen with intravenous administration of both prazosin and tamsulosin at doses over 3 micro g/kg, and these drugs completely blocked the tilt-induced blood pressure responses at 30 micro g/kg. On the other hand, these responses were still retained when KMD-3213 was administered intravenously at a dose up to 75 micro g/kg of KMD-3213. Moreover, KMD-3213 showed the highest uroselectivity of the test drugs. These results indicate that KMD-3213 is not likely to induce orthostatic hypotension and would be a useful compound for the treatment of urinary outlet obstruction in patients with benign prostatic hyperplasia. |
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Authors:
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Katsuyoshi Akiyama; Masachiyo Hora; Ryoichi Yamagishi; Makio Kitazawa |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Japanese journal of pharmacology Volume: 90 ISSN: 0021-5198 ISO Abbreviation: Jpn. J. Pharmacol. Publication Date: 2002 Oct |
Date Detail:
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Created Date: 2002-11-06 Completed Date: 2004-03-24 Revised Date: 2013-05-22 |
Medline Journal Info:
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Nlm Unique ID: 2983305R Medline TA: Jpn J Pharmacol Country: Japan |
Other Details:
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Languages: eng Pagination: 131-7 Citation Subset: IM |
Affiliation:
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Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan. katsuyoshi_akiyama@pharm.kissei.co.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic alpha-1 Receptor Antagonists* Adrenergic alpha-Antagonists / pharmacology* Animals Area Under Curve Blood Pressure / drug effects*, physiology Blood Vessels / metabolism Dose-Response Relationship, Drug Hypotension, Orthostatic / physiopathology Indoles / pharmacology* Injections, Intravenous Male Posture* Prazosin / pharmacology Rats Rats, Sprague-Dawley Receptors, Adrenergic, alpha-1 / metabolism Sulfonamides / pharmacology Time Factors Urethra / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic alpha-1 Receptor Antagonists; 0/Adrenergic alpha-Antagonists; 0/Indoles; 0/Receptors, Adrenergic, alpha-1; 0/Sulfonamides; 19216-56-9/Prazosin; CUZ39LUY82/silodosin; G3P28OML5I/tamsulosin |
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