Basic and clinical aspects of antimuscarinic agents used to treat overactive bladder

Yamada, Shizuo; Ito, Yoshihiko; Nishijima, Saori; Kadekawa, Katsumi; Sugaya, Kimio

doi:10.1016/j.pharmthera.2018.04.010

Cited by 82 publications

(82 citation statements)

References 183 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The current focus of pharmacological interventions for lower urinary tract symptoms has been primarily focused on muscarinic receptor antagonists due to the involvement of this receptor system in bladder voiding 43 . However, the use of antimuscarinics is associated with several side effects due to muscarinic receptor localisation throughout the body that limits their overall tolerability 44 .…”

Section: Discussionmentioning

confidence: 99%

Alterations in histamine responses between juvenile and adult urinary bladder urothelium, lamina propria and detrusor tissues

Štromberga

Chess-Williams

Moro

2020

Sci Rep

View full text Add to dashboard Cite

Russ chess-Williams & christian Moro * Inflammatory mediators may have a role in various lower urinary tract disorders. Histamine is known to induce significant increases in both the tension and frequency of spontaneous phasic contractions in both urothelium with lamina propria (U&LP) and detrusor muscle via the activation of H1 receptor in juvenile animal models. However, it is unclear whether age affects these contractile responses to histamine. This study assessed the histamine receptor subtypes mediating contraction in juvenile and adult porcine bladders and compared the urothelium with lamina propria and detrusor responses to histamine. Isolated tissue bath studies were conducted using strips of porcine U&LP and detrusor obtained from juvenile (6 months) and adult (3 years) animals exposed to histamine receptor agonists and antagonists. Treatment with histamine (100 µM) in U&LP of juvenile animals caused increases in baseline tension by 47.84 ± 6.52 mN/g (p < 0.001, n = 51) and by 50.76 ± 4.10 mN/g (p < 0.001, n = 55) in adult animals. Furthermore, the frequency of spontaneous phasic contractions was significantly enhanced in response to histamine in U&LP of both juvenile and adult tissues (p < 0.001 for both age groups). Treatment with an H2 agonist in U&LP of juvenile animals decreased baseline tension by 13.97 ± 3.45 mN/g (n = 12, p < 0.05), but had no effect in adult animals. Inhibition of H1 receptors resulted in significantly reduced contractile responses of U&LP and detrusor to histamine in both juvenile and adult animals (p < 0.05). Treatment with an H2 receptor antagonist significantly enhanced contractions in juvenile preparations (n = 10, p < 0.05) but had no effect in adult preparations (n = 8). In detrusor, treatment with histamine (100 µM) in juvenile tissues showed a significantly higher increase in baseline tension of 19.10 ± 4.92 mN/g (n = 51) when compared to adult tissues exhibiting increases of 8.21 ± 0.89 mN/g (n = 56, p < 0.05). The increases in the baseline tension were significantly inhibited by the presence of H1 receptor antagonists in both juvenile and adult detrusor preparations. Treatment with either the H2 receptor antagonist or agonist in detrusor had no effect on both juvenile and adult tissues. Therefore, the histamine receptor system may play an essential role in the maintenance of bladder function or in bladder dysfunction observed in some lower urinary tract disorders. Normal bladder function deteriorates throughout adult life, age appearing to have a direct effect on bladder sensation, contractility and the ability to postpone voiding 1. Ageing is associated with several changes that occur in the urinary bladder, such as a reduction in bladder capacity 2 and an increase in bladder sensitisation 3. It is also linked with marked increases in the prevalence of lower urinary tract symptoms, such as urinary frequency, voiding difficulties, decreased bladder contractions (as seen in underactive bladder) or uninhibited bladder contractions (as seen in overactive bladder) 1. Urin...

show abstract

Section: Discussionmentioning

confidence: 99%

Alterations in histamine responses between juvenile and adult urinary bladder urothelium, lamina propria and detrusor tissues

Štromberga

Chess-Williams

Moro

2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Also, decrease in urinary 8-OHdG and increase in urinary NOx, increased bladder wall expression of nNOS mRNA, and decreased bladder wall expression of iNOS, M3, and TRPV1 mRNA were also observed. Therefore, propiverine not only improved bladder dysfunction via its previously reported anti-muscarinic, Ca antagonist, and noradrenaline re-uptake inhibitory actions (8,17), but also by reducing inflamma-…”

Section: Referencesmentioning

confidence: 88%

“…Therefore, pelvic venous congestion may be one of the causes of pelvic ischemia, and might be related to lower urinary tract symptoms/diseases. Propiverine hydrochloride (propiverine) is an anticholinergic agent and Ca antagonist that is indicated for treatment of urinary urgency and/or urge incontinence due to involuntary bladder contractions (overactive bladder) (17). Since propiverine also increases the maximum urethral closing pressure by inhibiting noradrenaline re-uptake, it is effective for stress incontinence as well (8,16).…”

mentioning

confidence: 99%

Mechanisms underlying the effects of propiverine on bladder activity in rats with pelvic venous congestion and urinary frequency

Nishijima¹,

Sugaya²,

Kadekawa³

et al. 2019

Biomed. Res.

Self Cite

View full text Add to dashboard Cite

We investigated the mechanisms by which propiverine hydrochloride influenced bladder activity in rats with pelvic venous congestion (PC) and urinary frequency. To create PC rats, female rats were anesthetized with isoflurane and the bilateral common iliac veins and bilateral uterine veins were ligated. At 4 weeks after ligation, we assessed voiding behaviour, locomotor activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide metabolites (NOx). We also performed cystometry and measured mRNAs for nitric oxide synthase (NOS) and several receptors in the bladder wall. PC rats showed a decrease in locomotor activity and an increased frequency of urination. There was a decrease in endothelial NOS (eNOS), M3, and TRPV1 mRNA expression in the bladder wall, as well as an increase in inducible NOS (iNOS) mRNA. Administration of propiverine to PC rats increased locomotor activity to the level in sham rats, improved bladder function, decreased urinary 8-OHdG excretion, and increased urinary NOx excretion. In addition, propiverine increased neuronal NOS (nNOS) mRNA expression, and decreased expression of iNOS, M3 and TRPV1 mRNA in the bladder wall. Therefore, propiverine not only improved bladder dysfunction through its previously reported actions (anti-muscarinic effect, Ca antagonist effect, and inhibition of noradrenaline re-uptake), but also by reducing inflammation.

show abstract

“…In addition, significant side effects, such as dry mouth, constipation, and cognitive defects limit use of many antimuscarinic agents. 11,12 Lack of efficacy and side effects have resulted in low long-term treatment persistence (ranging from 5% to 47%). 13,14 Chemodenervation agents, such as botulinum toxin, may be limited by side effects, including urinary retention requiring catheterization.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the safety and potential activity of URO‐902 (hMaxi‐K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non‐neurogenic) overactive bladder syndrome and detrusor overactivity from two double‐blind, imbalanced, placebo‐controlled randomized phase 1 trials

Chai

Jacobs²,

Christ

et al. 2020

Neurourology and Urodynamics

View full text Add to dashboard Cite

Aims: Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO-902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit.Methods: ION-02 (intravesical instillation) and ION-03 (direct injection) were double-blind, placebo-controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION-02 participants received either 5000 µg or 10 000 µg URO-902, or placebo. ION-03 participants received either 16 000 or 24 000 µg URO-902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO-902 administration; secondary efficacy variables also were evaluated.---

show abstract

Basic and clinical aspects of antimuscarinic agents used to treat overactive bladder

Cited by 82 publications

References 183 publications

Alterations in histamine responses between juvenile and adult urinary bladder urothelium, lamina propria and detrusor tissues

Alterations in histamine responses between juvenile and adult urinary bladder urothelium, lamina propria and detrusor tissues

Mechanisms underlying the effects of propiverine on bladder activity in rats with pelvic venous congestion and urinary frequency

Contact Info

Product

Resources

About