Effects of a novel beta(3)-adrenoceptor agonist, AJ-9677, on relaxation of the detrusor muscle: an in vitro study.
OBJECTIVE
To examine the relaxant effects of AJ-9677, a novel beta(3)-adrenoceptor agonist, on the isolated rat, monkey and human detrusor muscle.


METHODS
The isolated detrusor strips of rats, monkeys and humans were mounted in organ baths containing Krebs solution. By the cumulative addition of beta-adrenoceptor agonists (isoproterenol, AJ-9677, CL 316,243 and salbutamol in rats; isoproterenol, AJ-9677 and CL 316,243 in monkeys and humans), concentration-relaxation curves were obtained. The maximal relaxation responses and pEC(50) values were calculated. In rats, concentration-relaxation curves to isoproterenol and AJ-9677 were obtained in the presence and absence of propranolol or SR 59230A.


RESULTS
Isoproterenol, AJ-9677, CL 316,243 and salbutamol induced concentration-dependent relaxation in rats. The rank order of their relaxing potency in the rat detrusor muscle was AJ-9677 > isoproterenol > CL 316,243 > salbutamol. Isoproterenol and AJ-9677 also produced a concentration-dependent relaxation with high potency in monkeys and humans, whilst CL 316,243 had low relaxing potency. According to the antagonist studies in rats, propranolol and SR 59230A caused a rightward shift of the concentration-relaxation curves to isoproterenol or AJ-9677, respectively.


CONCLUSIONS
AJ-9677 has a high relaxant potency on the rat, monkey and human detrusor smooth muscle, and it may have the potential to treat overactive bladder.
Otsuka
Atsushi
A
Department of Urology, Hamamatsu University School of Medicine, Kamakura, Kanagawa, Japan. otsuka@hama-med.ac.jp
Shinbo
Hitoshi
H
Hasebe
Ko
K
Matsumoto
Rikiya
R
Ozono
Seiichiro
S
D000085:Acetates / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004149:Dioxoles / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
C418363:((3-((2R)-(((2R)-3-chlorophenyl)-2-hydroxyethyl)amino)propyl)-1H-indol-7-yloxy)acetic acid; C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000085:Acetates; D000318:Adrenergic beta-Agonists; D004149:Dioxoles; D007211:Indoles; D011412:Propanolamines; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D011433:Propranolol; D007545:Isoproterenol