title: Co-administration of an α(1) -blocker improves the efficacy and safety of antimuscarinic agents in rats with detrusor overactivity.
abstract: OBJECTIVE
  To investigate the efficacy and safety of a combination treatment with α(1)-blockers and antimuscarinics for detrusor overactivity in rats.
  
  
  METHODS
  Rats with detrusor overactivity caused by a cerebral infarction were divided into four groups that received an i.v. administration of tamsulosin (0.1-1000 µg/kg); solifenacin (0.01-0.3 mg/kg); combined low doses of tamsulosin (0.008, 0.1 µg/kg) and solifenacin (0.01 mg/kg); or solifenacin (0.1, 0.3, 1.0 mg/kg) at 1-h intervals during the continuous administration of tamsulosin (0.01 µg/kg/h).
  
  
  RESULTS
  Both tamsulosin alone and solifenacin alone significantly increased bladder capacity in cerebral infarcted rats, but these effects were reduced in rats pretreated with resiniferatoxin. The combined low dose of tamsulosin and solifenacin resulted in a significant increase in bladder capacity compared to mono-administration of 0.01 mg/kg solifenacin (68.8 vs 19.8% of control value, respectively). In the group receiving solifenacin at 1-h intervals, solifenacin dose-dependently decreased bladder contraction duration and a significant reduction in bladder contraction pressure (by 35.0% of control value) was found at the highest dose (1.0 mg/kg). However, no reduction in bladder contraction duration was found even at the highest dose of solifenacin when co-administered with tamsulosin.
  
  
  CONCLUSIONS
  α(1)-Blockers and antimuscarinic agents have an additive ameliorative effect on detrusor overactivity when co-administered at low doses. α(1)-Blockers prevent the reduction in bladder contraction duration induced by a high-dose administration of antimuscarinic agents.
authors: Department of Urology, Faculty of Medical Science, University of Fukui, Eiheiji, Fukui, Japan.
authors: Keiko
authors: K
authors: Nagase
authors: Hideaki
authors: H
authors: Ito
authors: Yoshitaka
authors: Y
authors: Aoki
authors: Kazuya
authors: K
authors: Tanase
authors: Hironobu
authors: H
authors: Akino
authors: Osamu
authors: O
authors: Yokoyama
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D009119:Muscle Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011812:Quinuclidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069464:Solifenacin Succinate; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D000077409:Tamsulosin; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D001743:Urinary Bladder / Q000473:pathology / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D004224:Diterpenes; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D013449:Sulfonamides; D044005:Tetrahydroisoquinolines; C024353:resiniferatoxin; D000077409:Tamsulosin; D000069464:Solifenacin Succinate