RT Journal Article
SR Electronic
T1 Effect of (<em>R</em>)-2-(2-Aminothiazol-4-yl)-4′-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} Acetanilide (YM178), a Novel Selective β<sub>3</sub>-Adrenoceptor Agonist, on Bladder Function
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 642
OP 647
DO 10.1124/jpet.106.115840
VO 321
IS 2
A1 Toshiyuki Takasu
A1 Masashi Ukai
A1 Shuichi Sato
A1 Tetsuo Matsui
A1 Itsuro Nagase
A1 Tatsuya Maruyama
A1 Masao Sasamata
A1 Keiji Miyata
A1 Hisashi Uchida
A1 Osamu Yamaguchi
YR 2007
UL http://jpet.aspetjournals.org/content/321/2/642.abstract
AB We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4′-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human β3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human β1- and β2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective β-AR agonist) was 0.8 for human β3-ARs, 0.1 for human β1-ARs, and 0.1 for human β2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (β3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10–6 M CCh were 5.1 and 1.4 μM, respectively, whereas those in human bladder strips precontracted with 10–7 M CCh were 0.78 and 0.28 μM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence. The American Society for Pharmacology and Experimental Therapeutics