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.

CONCLUSION:

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: Keiko Nagase, Hideaki Ito, Yoshitaka Aoki, Kazuya Tanase, Hironobu Akino, Osamu Yokoyama
• Journal: International journal of urology : official journal of the Japanese Urological Association (Int J Urol) Vol. 18 Issue 12 Pg. 836-43 (Dec 2011) ISSN: 1442-2042 [Electronic] Australia
• PMID: 21995543 (Publication Type: Journal Article)
• Copyright: © 2011 The Japanese Urological Association.

Chemical References

• Adrenergic alpha-1 Receptor Antagonists
• Diterpenes
• Muscarinic Antagonists
• Quinuclidines
• Sulfonamides
• Tetrahydroisoquinolines
• resiniferatoxin
• Tamsulosin
• Solifenacin Succinate

Topics

• Adrenergic alpha-1 Receptor Antagonists (pharmacology, therapeutic use)
• Analysis of Variance
• Animals
• Disease Models, Animal
• Diterpenes (pharmacology)
• Drug Therapy, Combination
• Female
• Infarction, Middle Cerebral Artery (complications)
• Muscarinic Antagonists (pharmacology, therapeutic use)
• Muscle Contraction (drug effects)
• Organ Size (drug effects)
• Quinuclidines (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Solifenacin Succinate
• Statistics, Nonparametric
• Sulfonamides (pharmacology, therapeutic use)
• Tamsulosin
• Tetrahydroisoquinolines (pharmacology, therapeutic use)
• Urinary Bladder (pathology, physiopathology)
• Urinary Bladder, Overactive (drug therapy, etiology)