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Urolithiasis
Published in: Urolithiasis 6/2005

01-12-2005 | Original Paper

The potency of KUL-7211, a selective ureteral relaxant, in isolated canine ureter: comparison with various spasmolytics

Authors: Isao Wanajo, Yoshitaka Tomiyama, Mariko Tadachi, Mamoru Kobayashi, Yoshinobu Yamazaki, Masami Kojima, Nobuo Shibata

Published in: Urolithiasis | Issue 6/2005

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Abstract

We compared the potency of a selective ureteral relaxant KUL-7211 (β2/β3-adrenoceptor agonist; (-)-2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenyloxy]acetic acid) with those of various spasmolytics on contractions in isolated canine ureteral preparations. Drug effects were evaluated on the tonic contraction induced by KCl (80 mM) and on spontaneous, 1×10−5 M phenylephrine-, and 1×10−6 M PGF2α-induced rhythmic contractions in isolated canine ureteral preparations using a functional experimental technique. The potencies (pD2 value) of the following drugs were compared: KUL-7211, tamsulosin (an α1A/1D-adrenoceptor antagonist), prazosin (an α1-adrenoceptor antagonist), verapamil (a Ca2+-channel blocker), butylscopolamine (a nonselective muscarinic antagonist), and papaverine (a phosphodiesterase inhibitor). The rank order of relaxing potencies against KCl-induced tonic contraction was KUL-7211 (6.60)>tamsulosin(5.90)>verapamil(5.70)>papaverine(4.88)>prazosin (4.54). The rank order of potencies for reductions in spontaneous rhythmic contractions was KUL-7211 (6.80)>verapamil(6.12)>papaverine(5.05). Conversely, high concentrations of the two α-adrenoceptor antagonists (tamsulosin and prazosin) and of butylscopolamine enhanced the spontaneous contractions, although at low concentrations (up to 1×10−6 M) they had no significant effects. For suppression of spasmogen-induced rhythmic contractions, the rank order of potencies was, against phenylephrine-induced contractions: KUL-7211 (6.95)>tamsulosin(6.26)>prazosin(5.68)>verapamil(5.64)>papaverine (5.03), and against PGF2α-induced contractions: KUL-7211 (7.05)>verapamil(6.70)>papaverine (5.27). Our results suggest that in dogs, the β2/β3-adrenoceptor agonist KUL-7211 is the most efficacious ureteral relaxant among the spasmolytics tested against various contractions. Possibly, KUL-7211 might be useful for promoting stone passage and relieving ureteral colic in urolithiasis patients.
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Metadata
Title
The potency of KUL-7211, a selective ureteral relaxant, in isolated canine ureter: comparison with various spasmolytics
Authors
Isao Wanajo
Yoshitaka Tomiyama
Mariko Tadachi
Mamoru Kobayashi
Yoshinobu Yamazaki
Masami Kojima
Nobuo Shibata
Publication date
01-12-2005
Publisher
Springer-Verlag
Published in
Urolithiasis / Issue 6/2005
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI
https://doi.org/10.1007/s00240-005-0475-5

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