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The combination of a β-adrenoceptor agonist and an antimuscarinic agent was revealed to be more effective than monotherapy for patients with overactive bladder and in animal models. However, its influence on voiding functions has not been well documented. Therefore, during intermittent-cystometry, we studied the effects of vibegron (a novel β-adrenoceptor agonist) and imidafenacin (an antimuscarinic agent) alone to determine their dose levels for the combination study. Then, the effects of the combination on voiding functions were investigated in urethane-anesthetized rats (1.0 g/kg s.c.). Independently, vibegron (0.3-3 mg/kg, i.v.) and imidafenacin (0.001 and 0.003 mg/kg, i.v.) dose-dependently increased bladder capacity and voided volume, without affecting voiding functions such as residual volume, voiding efficiency, and micturition pressure. However, vibegron also increased bladder compliance. The combination of vibegron (3 mg/kg) and imidafenacin (0.003 mg/kg) significantly increased bladder capacity and voided volume when compared to those with monotherapy using each individually. The combination did not change residual volume, voiding efficiency, and micturition pressure, compared to those in the vehicle group. We identified no responses in resiniferatoxin (RTX)-treated rats, as opposed to those identified after administering vibegron (3 mg/kg), imidafenacin (0.003 mg/kg), or both to non-RTX-treated rats. These outcomes might have resulted from the combination of the increased effect of vibegron on bladder compliance and the inhibitory effect of both vibegron and imidafenacin on the activation of bladder afferent nerves.
This article was published in the following journal.
Name: European journal of pharmacology
To investigate bladder function patterns following cystostomy and determine the best time window for cystometric evaluation of bladder function in conscious rats.
Previous patient surveys have shown that patients with spinal cord or cauda equina injuries prioritize recovery of bladder function. The authors sought to determine if nerve transfer after long-term d...
To test the hypothesis that naftopidil prolongs intercontraction intervals in rats undergoing chronic stress as observed in previous animal models, voiding behavior and bladder function were measured ...
Distigmine bromide (distigmine) is a reversible carbamate cholinesterase (ChE) inhibitor that is used to treat myasthenia gravis. In Japan, it is also used as a remedy for urination disorder (underact...
To determine the effects of early sacral neuromodulation (SNM) and pudendal neuromodulation (PNM) on lower urinary tract (LUT) function, minipigs with complete spinal cord injury (cSCI) were analyzed....
This study will assess the long-term safety of vibegron when dosed up to 52 weeks in men with overactive bladder (OAB) symptoms on pharmacological therapy for Benign Prostatic Hyperplasia ...
This study is designed to evaluate the safety, tolerability, and efficacy of vibegron administered once daily in patients with OAB.
This study is designed to evaluate the safety, tolerability, and efficacy of vibegron administered once daily in patients with OAB for up to 52 weeks.
This study will assess the safety, tolerability, and efficacy of vibegron compared with placebo in men with overactive bladder (OAB) symptoms on pharmacological therapy for benign prostati...
Objective of this study was confirmation on non-inferiority and validation of similar safety profile of new anti-muscarinic medicinal product Uritos® (Imidafenacin) in comparison with oth...
Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen.
Aromatic diamine used in the plastics industry as curing agent for epoxy resins and urethane rubbers. It causes bladder, liver, lung, and other neoplasms.
Combination of procedures, methods, and tools by which a policy, program, or project may be judged as to its potential effects on the health of a population, and the distribution of those effects within the population.
A HERNIA-like condition in which the weakened pelvic muscles cause the URINARY BLADDER to drop from its normal position. Fallen urinary bladder is more common in females with the bladder dropping into the VAGINA and less common in males with the bladder dropping into the SCROTUM.
Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.
Non-invasive bladder cancer is a cancer that is only in the inner lining of the bladder. Invasive bladder cancer is cancer that has spread into the deeper walls of the bladder. When the cancer has spread outside the bladder to other parts of the body, th...