PMID- 22981677
OWN - NLM
STAT- MEDLINE
DCOM- 20130506
LR  - 20131121
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Linking)
VI  - 62
IP  - 6
DP  - 2012 Dec
TI  - Effects of mirabegron, a novel beta3-adrenoceptor agonist, on primary bladder 
      afferent activity and bladder microcontractions in rats compared with the effects 
      of oxybutynin.
PG  - 1165-73
LID - S0302-2838(12)01009-3 [pii]
LID - 10.1016/j.eururo.2012.08.056 [doi]
AB  - BACKGROUND: Mirabegron is the first beta3-adrenoceptor agonist that is clinically 
      effective for overactive bladder. OBJECTIVE: The effects of mirabegron on primary 
      bladder mechanosensitive single-unit afferent activities (SAAs) and bladder 
      microcontractions were evaluated and compared with the effects of oxybutynin. 
      DESIGN, SETTING, AND PARTICIPANTS: Female Sprague-Dawley rats were anesthetized. 
      The SAAs generated from left L6 dorsal roots were identified by electrical 
      stimulation of the left pelvic nerve and bladder distension. Nerves with 
      conduction velocities (CVs) >2.5 m/s were designated as Adelta-fibers, and nerves 
      with CVs<2.5 m/s were designated as C-fibers. OUTCOME MEASUREMENTS AND 
      STATISTICAL ANALYSIS: Two measurements were performed in separate animals. First, 
      after measuring the baselines of SAA during constant filling cystometry, the 
      procedure was repeated with each intravenous administration of mirabegron at 
      three doses-0.1, 0.3, and 1.0mg/kg-cumulatively. Second, the bladder was filled 
      with saline until the intravesical pressure reached 30 cm H(2)O and was kept 
      under an isovolumetric condition; then the recording was performed for 5 min with 
      vehicle and mirabegron or oxybutynin administrated intravenously. RESULTS AND 
      LIMITATIONS: A total of 74 single-unit afferent fibers were isolated from 55 rats 
      (Adelta-fibers: n=34; C-fibers: n=40). SAAs of both Adelta-fibers and C-fibers in 
      response to bladder filling significantly decreased after mirabegron 
      administration in a dose-dependent manner, which was more remarkable for 
      Adelta-fibers. During an isovolumetric condition of the bladder, the mean bladder 
      pressure and the number of microcontractions decreased after mirabegron 
      administration, whereas these parameters did not change with oxybutynin 
      administration. SAAs of Adelta-fibers were significantly decreased by mirabegron 
      administration at both 0.3 and 1mg/kg, whereas SAAs of C-fibers decreased only at 
      1mg/kg. In contrast, oxybutynin (1mg/kg) did not alter either type of SAA. 
      CONCLUSIONS: The present study demonstrates that mirabegron can inhibit 
      mechanosensitive bladder afferent activity, especially of Adelta-fibers, which may be 
      related to suppression of bladder microcontractions.
CI  - Copyright (c) 2012 European Association of Urology. Published by Elsevier B.V. All 
      rights reserved.
FAU - Aizawa, Naoki
AU  - Aizawa N
AD  - Department of Continence Medicine, The University of Tokyo Graduate School of 
      Medicine, Tokyo, Japan.
FAU - Homma, Yukio
AU  - Homma Y
FAU - Igawa, Yasuhiko
AU  - Igawa Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120905
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Acetanilides)
RN  - 0 (Adrenergic beta-3 Receptor Agonists)
RN  - 0 (Mandelic Acids)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Thiazoles)
RN  - K9P6MC7092 (oxybutynin)
RN  - MVR3JL3B2V (mirabegron)
SB  - IM
MH  - Acetanilides/*pharmacology
MH  - Adrenergic beta-3 Receptor Agonists/*pharmacology
MH  - Animals
MH  - Female
MH  - Mandelic Acids/*pharmacology
MH  - Muscarinic Antagonists/*pharmacology
MH  - Muscle Contraction/*drug effects/physiology
MH  - Neurons, Afferent/*drug effects/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thiazoles/*pharmacology
MH  - Urinary Bladder/*drug effects/innervation/*physiology
EDAT- 2012/09/18 06:00
MHDA- 2013/05/07 06:00
CRDT- 2012/09/18 06:00
PHST- 2012/06/27 00:00 [received]
PHST- 2012/08/27 00:00 [accepted]
PHST- 2012/09/18 06:00 [entrez]
PHST- 2012/09/18 06:00 [pubmed]
PHST- 2013/05/07 06:00 [medline]
AID - S0302-2838(12)01009-3 [pii]
AID - 10.1016/j.eururo.2012.08.056 [doi]
PST - ppublish
SO  - Eur Urol. 2012 Dec;62(6):1165-73. doi: 10.1016/j.eururo.2012.08.056. Epub 2012 
      Sep 5.