The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity
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The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity. / Svalø, Julie; Nordling, Jørgen; Bouchelouche, Kirsten; Andersson, Karl-Erik; Korstanje, Cees; Bouchelouche, Pierre; Svalø, Julie .
In: European Journal of Pharmacology, Vol. 699, No. 1-3, 15.01.2013, p. 101-5.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity
AU - Svalø, Julie
AU - Nordling, Jørgen
AU - Bouchelouche, Kirsten
AU - Andersson, Karl-Erik
AU - Korstanje, Cees
AU - Bouchelouche, Pierre
AU - Svalø, Julie
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2013/1/15
Y1 - 2013/1/15
N2 - β(3)-Adrenoceptors are major players in detrusor relaxation and have been suggested as a new putative target for the treatment of overactive bladder syndrome. We determined the effects of mirabegron (YM178), a novel β(3)-adrenoceptor agonist, on carbachol-induced tone in isolated human detrusor preparations from patients with bladder outflow obstruction (BOO) with and without detrusor overactivity (DO), and from patients with normal bladder function. We compared the effects to those of isoprenaline, a non-selective β-adrenoceptor agonist. Detrusor specimens were obtained from patients with benign prostatic hyperplasia undergoing cystoscopy and from patients undergoing radical prostatectomy/cystectomy (in total 33 donors). Detrusor contractility was evaluated by organ bath studies and strips were incubated with carbachol (1μM) to induce and enhance tension. Both mirabegron and isoprenaline reduced carbachol-induced tone in tissues from all groups. Isoprenaline decreased tension with higher potency than mirabegron in normal, BOO and BOO+DO detrusor strips with pIC(50) values of 7.49 ± 0.16 vs. 6.23 ± 0.26 (P=0.0002), 6.89 ± 0.34 vs. 6.04 ± 0.31 (P=0.01), and 6.57 ± 0.20 vs. 5.41 ± 0.08 (P<0.0001, n=4), respectively. The maximal relaxant effect of isoprenaline and mirabegron in the normal, BOO and BOO+DO detrusor was 37.7 ± 14.4% and 36.1 ± 23.3%, 14.4 ± 12.2% vs. 33.4 ± 21.0% and 18.3 ± 10.0% vs. 28.3 ± 12.2% (n=4, P>0.05), respectively. Mirabegron and isoprenaline reduced carbachol-induced tone in both normal bladders and obstructed bladder with and without DO. Isoprenaline had higher potency than mirabegron, but the efficacy of mirabegron effect was the same as that of isoprenaline.
AB - β(3)-Adrenoceptors are major players in detrusor relaxation and have been suggested as a new putative target for the treatment of overactive bladder syndrome. We determined the effects of mirabegron (YM178), a novel β(3)-adrenoceptor agonist, on carbachol-induced tone in isolated human detrusor preparations from patients with bladder outflow obstruction (BOO) with and without detrusor overactivity (DO), and from patients with normal bladder function. We compared the effects to those of isoprenaline, a non-selective β-adrenoceptor agonist. Detrusor specimens were obtained from patients with benign prostatic hyperplasia undergoing cystoscopy and from patients undergoing radical prostatectomy/cystectomy (in total 33 donors). Detrusor contractility was evaluated by organ bath studies and strips were incubated with carbachol (1μM) to induce and enhance tension. Both mirabegron and isoprenaline reduced carbachol-induced tone in tissues from all groups. Isoprenaline decreased tension with higher potency than mirabegron in normal, BOO and BOO+DO detrusor strips with pIC(50) values of 7.49 ± 0.16 vs. 6.23 ± 0.26 (P=0.0002), 6.89 ± 0.34 vs. 6.04 ± 0.31 (P=0.01), and 6.57 ± 0.20 vs. 5.41 ± 0.08 (P<0.0001, n=4), respectively. The maximal relaxant effect of isoprenaline and mirabegron in the normal, BOO and BOO+DO detrusor was 37.7 ± 14.4% and 36.1 ± 23.3%, 14.4 ± 12.2% vs. 33.4 ± 21.0% and 18.3 ± 10.0% vs. 28.3 ± 12.2% (n=4, P>0.05), respectively. Mirabegron and isoprenaline reduced carbachol-induced tone in both normal bladders and obstructed bladder with and without DO. Isoprenaline had higher potency than mirabegron, but the efficacy of mirabegron effect was the same as that of isoprenaline.
KW - Acetanilides
KW - Adrenergic beta-3 Receptor Agonists
KW - Adrenergic beta-Agonists
KW - Aged
KW - Aged, 80 and over
KW - Carbachol
KW - Humans
KW - Inhibitory Concentration 50
KW - Isoproterenol
KW - Male
KW - Middle Aged
KW - Muscle Contraction
KW - Thiazoles
KW - Urinary Bladder
KW - Urinary Bladder Neck Obstruction
KW - Urinary Bladder, Overactive
U2 - 10.1016/j.ejphar.2012.11.060
DO - 10.1016/j.ejphar.2012.11.060
M3 - Journal article
C2 - 23246623
VL - 699
SP - 101
EP - 105
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -
ID: 128887469