PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “overactive bladder”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources

Tools to study beta3-adrenoceptors.

Beta(3)-adrenoceptors mediate some of the effects of catecholamines on tissues such as blood vessels or the urinary bladder and are putative targets for the treatment of diseases such as the overactive bladder syndrome. Progress in the understanding of the presence, function, and regulation of beta(3)-adrenoceptors has been hampered by a lack of highly specific tools. "Classical" beta(3)-adrenoceptor agonists such as BRL 37,344 [(R*, R*)-(+/-)-4[2-[(3-chlorophenyl)-2-hydroxyethyl) amino] propyl] phenoxyacetic acid] and CGP 12,177 [(+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one] are only partial agonists in many settings, have limited selectivity over other beta-adrenoceptor subtypes, and may additionally act on receptors other than beta-adrenoceptors. More efficacious and more selective agonists have been reported and, in some cases, are in clinical development but are not widely available for experimental studies. The widely used antagonist SR 59,230 [3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanoloxalate] is not selective for beta(3)-adrenoceptors, at least in humans, and may actually be a partial agonist. Radioligands, which are suitable either for the selective labeling of beta(3)-adrenoceptors or for the nonselective labeling of all beta-adrenoceptor subtypes, are also missing. beta(3)- and beta(1)/beta(2) double knockout mice have been reported, but their usefulness for extrapolations in humans is questionable based upon major differences between humans and rodents with regard to the ligand recognition and expression profiles of beta(3)-adrenoceptors. While the common availability of more selective agonists and antagonists at the beta(3)-adrenoceptor is urgently awaited, the limitations of the currently available tools need to be considered in studies of beta(3)-adrenoceptor for the time being.

Adrenergic beta-3 Receptor Agonists↗

Bladder dysfunction in children with bilateral single ectopic ureters.

BACKGROUND: Single ectopic ureters are a rare malformation in children. Therapy consists of ureteral reimplantation. However, in case of bilateral single ectopic ureters, subsequent malformation of the bladder trigone and bladder neck may result in additional voiding dysfunction, and ureteral reimplantation alone may not solve the urologic problems. METHODS: The authors report their experience with 2 girls, in whom bilateral single ectopic ureters were treated by ureteral reimplantation in early childhood and who did not gain adequate bladder control during following years. RESULTS: Videourodynamic evaluation was done in both girls. No bladder overactivity was found during the urodynamic studies. However, cystography showed a widely open bladder neck during filling with no sufficient bladder neck closure shown by urethral pressure profile studies. When blocking the bladder outlet by balloon catheters, adequate bladder filling volume was achieved. Incontinence was cured by implantation of an AMS 800 artificial sphincter system in a 10-year-old girl. A 7-year-old girl was regarded to be too young for sphincter implantation and is waiting for surgery within the next years. CONCLUSION: Insufficient development of trigone and bladder neck with subsequent urinary incontinence has to be kept in mind when deciding on surgical procedures in children with bilateral single ectopic ureters.

Abnormalities, Multiple↗

The future of bladder control-intravesical drug delivery, a pinch of pepper, and gene therapy.

The incidence of urinary incontinence and overactive bladder problems will continue to grow as the population ages. Future treatments are likely to include an implantable drug delivery system, gene therapy, and the intravesical use of the vallinoids capsaicin and resiniferatoxin (RTX). An understanding of the urothelium is essential for effective design of these therapies. Intravesical anticholinergic drug treatment is currently not widely used, but intravesical pumps are under development to provide less cumbersome treatment methods and will provide nonsurgical options for patients who cannot tolerate oral anticholinergic agents. Research on the use of capsaicin as an intravesicular drug has had limited success, but trials have confirmed the efficacy of intravesical capsaicin for detrusor hyperreflexia. RTX is as effective as capsaicin but without side effects, such as pain and inflammatory neuropeptide release. RTX treatment may eliminate the need for surgical and other drug treatments of lower urinary tract dysfunction in patients with spinal cord injuries. Gene therapy will change the practice of urology by addressing the deficiencies that cause symptoms rather than attacking the symptoms themselves.

Journal Article↗

Urodynamic effects of the K+ channel (KCNQ) opener retigabine in freely moving, conscious rats.

PURPOSE: Retigabine is a novel anticonvulsant drug that not only augments gamma-aminobutyric acid mechanisms, but also opens voltage gated K+ channels (KCNQ). In this study we investigated the effects of retigabine on detrusor activity in rats. MATERIALS AND METHODS: To conscious, female Sprague-Dawley rats undergoing continuous cystometry retigabine was given intravenously (0.5, 1 and 5 mg/kg(-1)). The KCNQ channel blocker linopirdine was given intravenously (2 mg/kg(-1)) 5 minutes prior to retigabine (1 mg/kg(-1)). In addition, retigabine was given intracerebroventricularly (1, 5 and 10 microg) and intravesically (100, 500 and 1,000 ng ml(-1)). The effects of the drug (intravesical administration) on capsaicin induced bladder overactivity were also tested. RESULTS: Retigabine given intravenously (1 mg/kg(-1)) decreased baseline and maximal bladder pressures, increased voided and infused volumes, and increased voiding intervals. Retigabine (10 microg) given intracerebroventricularly decreased baseline pressure and increased voided and infused volumes as well as voiding intervals. However, bladder pressures were not significantly affected. Intravesical retigabine (1,000 ng.ml(-1)) decreased maximal bladder pressure, increased voided and infused volumes, and increased voiding intervals. Given intravesically for 30 minutes prior to intravesical capsaicin (30 microM) instillation retigabine (1,000 ng.ml(-1)) decreased the detrusor overactivity induced by capsaicin. The KNCQ channel blocker linopirdine (2 mg/kg(-1)) completely blocked the effects of intravenous retigabine (1 mg/kg(-1)). CONCLUSIONS: Retigabine given intravenously, intracerebroventricularly and intravesically increased micturition volume and voiding intervals and, when given intravesically, it decreased capsaicin induced detrusor overactivity, suggesting that KCNQ channels can be interesting targets for drugs aiming at micturition control. Retigabine may be a candidate to test as a treatment for detrusor overactivity in humans.

Animals↗

Quality of life changes in patients with neurogenic versus idiopathic detrusor overactivity after intradetrusor injections of botulinum neurotoxin type A and correlations with lower urinary tract symptoms and urodynamic changes.

OBJECTIVE: Little published data exist on the effect of intradetrusor botulinum neurotoxin type A (BoNT/A) on the quality of life (QOL) of patients with overactive bladder. We examined post-BoNT/A QOL changes of patients with neurogenic detrusor overactivity (NDO) in comparison to those with idiopathic detrusor overactivity (IDO), and their correlations with respective changes in lower urinary tract symptoms (LUTS) and urodynamic parameters. METHODS: Patients with urodynamically proven intractable DO were assessed for changes in QOL 4 and 16 wk after treatment with intradetrusor BOTOX injections (NDO 300U; IDO 200U) using the short forms of the Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7). Percent changes in total QOL score were correlated to respective changes in clinical parameters recorded by bladder diaries and voiding cystometry. RESULTS: Forty-eight treated patients (32 NDO, 16 IDO) had QOL data in at least one follow-up. Highly significant decreases (p < 0.0001) in mean +/- standard error QOL score at 4 wk were maintained at 16 wk for both the NDO and IDO subgroups. Percent improvement in QOL score was similar for NDO versus IDO at 4 (67.6 +/- 4.5 versus 70.3 +/- 7.7, p = 0.74) and 16 wk (65.2 +/- 5.5 versus 71.9 +/- 8.8, p = 0.51). Percent changes in QOL score of the whole patient group correlated with changes in 24-h micturition frequency, number of voids associated with urgency, and number of urge incontinence episodes, but not with urodynamic parameters. CONCLUSIONS: Intradetrusor BoNT/A produces comparable, significant improvements in the QOL of patients with either NDO or IDO at least up to 16 wk after treatment. In contrast to urodynamic parameters, changes in LUTS appear to be the major determinants of improvements in the patients' QOL.

Adult↗

Urgency of voiding and abdominal pressure transmission in women with mixed urinary incontinence.

AIMS: To ascertain whether abdominal pressure transmission (a.p.t.) to the urethra would be affected by urgency of voiding in women with mixed urinary incontinence. METHODS: We urodynamically assessed 80 consecutive women. Group 1 (n = 40), with stress incontinence, had stable bladders and no urgency. Group 2 (n = 40), with mixed (stress + urge) incontinence and overactive bladders, were split into Groups 2A (n = 20) and 2B (n = 20) according to the delay time of urgent void at cystometry (CMG) equating at least 2 min (taken as an index of moderate urgency) or, respectively, less than 2 min (taken as an index of severe urgency). Nonparametric statistics checked for significant differences in a.p.t. and in pelvic floor (peri-urethral) muscle strength level. We defined a.p.t. at stress (cough) urethral pressure profilometry (UPP) by the pressure transmission ratio (PTR). Pelvic floor muscle strength was defined at "holding" UPP by the maximum urethral pressure developed during attempts "to hold urine" (hMUP). RESULTS: PTR was reduced in all women, but PTR (and hMUP) proved relatively higher in Group 2, though nonsignificantly different values of PTR (and hMUP) were seen in Groups 2B and 1. CONCLUSIONS: Transmission of abdominal pressure to the urethra was reduced in all of the incontinent women. The mixed incontinence group, however, had a relatively less reduced (active component of) a.p.t., most likely dependent on a greater pelvic floor (peri-urethral) muscle strength level secondary to frequent contractions in response to urgency. Yet, of the same mixed incontinence patients, those with the most severe urgency degrees had relatively low pelvic floor (peri-urethral) muscle strength levels (eventually resulting from muscle fatigue? or primarily due to peri-urethral tissue atrophy?), which prevented (the active component of) a.p.t. from increasing.

Abdomen↗

Characterization of muscarinic receptor binding and inhibition of salivation after oral administration of tolterodine in mice.

The current study was undertaken to characterize the effects of oral administration of tolterodine on muscarinic receptor binding in the bladder and submaxillary gland and on salivation in mice. In the in vitro experiment, tolterodine and its metabolite (5-hydroxymethyl metabolite: 5-HM) competed concentration-dependently with [N-methyl-(3)H]-scopolamine ([(3)H]NMS) in the mouse bladder, submaxillary gland and heart, and the potencies of both agents were greater than that of oxybutynin. After oral administration of tolterodine (6.31, 21.0 micromol/kg) and oxybutynin (76.1 micromol/kg), there was a dose and time-dependent increase in K(d) values for specific [(3)H]NMS binding in the bladder, prostate, submaxillary gland, heart, colon and lung, compared with control values, suggesting significant muscarinic receptor binding in each tissue. The K(d) increase in each tissue by oral oxybutynin reached a maximum value of 0.5 h after oral administration and then rapidly declined, while that by tolterodine was greatest 2 h after the administration and it was maintained for at least 6 or 12 h, depending on the dose and on the tissue. Thus, muscarinic receptor binding of oral tolterodine was slower in onset and of a longer duration than that of oxybutynin. Also, oral oxybutynin showed relatively greater receptor binding in the submaxillary gland as compared with other tissues, but such high selectivity to the exocrine gland muscarinic receptors was not observed by oral tolterodine. Oral administration of tolterodine and oxybutynin reduced significantly the pilocarpine-induced salivary secretion in mice, and the attenuation of oral tolterodine appeared more slowly and it was more persistent than that of oral oxybutynin. The antagonistic effect of oral tolterodine on the dose-response curves to pilocarpine was significantly weaker than that of oxybutynin. These data suggest that oral tolterodine, compared with the case of oral oxybutynin, binds more selectively to muscarinic receptors in the mouse bladder than in the submaxillary gland, which may be advantageous in treating patients with overactive bladder.

Administration, Oral↗

A novel pyrrole derivative, NS-8, suppresses the rat micturition reflex by inhibiting afferent pelvic nerve activity.

OBJECTIVE: To investigate the suppressive effect of a newly synthesized compound, 2-amino-3-cyano-5-(2-fluorophenyl)-4-methylpyrrole (NS-8), on micturition, and its mode and sites of action in rats. MATERIALS AND METHODS: Female rats were anaesthetized with urethane, and isovolumetric bladder contractions and cystometrograms recorded. The pelvic afferent discharges from the bladder were also monitored. RESULTS: In the cystometric study, NS-8 increased the bladder capacity without affecting the maximum bladder contraction pressure, an effect unlike that of currently used anticholinergic drugs for the overactive bladder, which commonly decrease the maximum bladder contraction pressure. Intravesical and intravenous injection of NS-8 inhibited isovolumetric bladder contractions in a dose-dependent manner without affecting their amplitude, whereas intracerebroventricular injection with NS-8 had no such effect. During the urine storage phase of the cystometrogram, NS-8 decreased the discharge rate of the afferent pelvic nerve from the bladder, in association with a decrease in the increase in intravesical pressure. CONCLUSION: NS-8 suppressed the micturition reflex by decreasing afferent pelvic nerve activity. Activation of calcium-sensitive potassium channel of the bladder may be responsible for such an effect. This agent has the potential to treat patients with urinary frequency and incontinence.

Animals↗

Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity.

PURPOSE: We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity. MATERIALS AND METHODS: In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects. RESULTS: After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events. CONCLUSIONS: Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects.

Adult↗

Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional.

1. The parasympathetic nervous system is responsible for maintaining normal bladder function, contracting the bladder smooth muscle (detrusor) and relaxing the bladder outlet during micturition. 2. Contraction of the bladder involves direct contraction via M3 receptors and an indirect 're-contraction' via M2-receptors whereby a reduction in adenylate cyclase activity reverses the relaxation induced by beta-adrenoceptor stimulation. 3. Muscarinic receptors are also located on the epithelial lining of the bladder (urothelium) where they induce the release of a diffusible factor responsible for inhibiting contraction of the underlying detrusor smooth muscle. The factor remains unidentified but is not nitric oxide, a cyclooxygenase product or adenosine triphosphate. 4. Finally, muscarinic receptors are also located prejunctionally in the bladder on cholinergic and adrenergic nerve terminals, where M1-receptors facilitate transmitter release and M2 or M4-receptors inhibit transmitter release. 5. In pathological states, changes may occur in these receptor systems resulting in bladder dysfunction. Muscarinic receptor antagonists are the main therapeutic agents available for treatment of the overactive bladder, but whether their therapeutic effect involves actions at all three locations (detrusor, prejunctional, urothelial) has yet to be established.

Animals↗

Effect of transvaginal stimulation in the treatment of detrusor instability.

INTRODUCTION: Early research on implantable electrodes for transvaginal stimulation had high rates of complications and mechanical failures. Today's nonimplantable devices are safe for short-term or long-term use. This study evaluated an intermittent short-term transvaginal stimulation program for treatment of bladder overactivity. METHODS: Fifteen women who ranged in age from 22 to 96 years and had bladder instability were enrolled into this noncontrolled, open, clinical evaluation program. Six to 10 biweekly office sessions were followed by use of a home unit twice daily for approximately 6 weeks. RESULTS: Results were based on patients' voiding diaries. All 15 completed the study, and 73% were satisfied with the results. On pretrial urodynamic examination nine patients had sensory urgency, and six patients had involuntary contractions. All tolerated therapy without side effects. Two women had slight vaginal discomfort because of vaginal narrowing. Urinary frequency, urgency, and nocturia were significantly decreased. Seven women reported 75% or more improvement; four women reported 50% to 75% improvement. Three women required a second office treatment series. DISCUSSION: The results of this study support findings of previous researchers, although the follow-up time frame of the study was short. Most of these patients (N = 11 of 15) wished to continue transvaginal stimulation. When three women discontinued home treatments, symptoms recurred in 1 to 3 months. The exact cause is unclear, but scar tissue as a result of previous pelvic operations may have contributed to the problem. The second course of treatment had positive results. Intermittent therapy in these cases is recommended. Transvaginal stimulation should be considered for treatment for urinary incontinence because the device is easily used and adjusted by the patient, patients may be very compliant, and results are satisfactory and at least similar to those attained with drug therapy.

Adult↗

Reflex interaction between the proximal urethra and the bladder. A clinical experimental study.

OBJECTIVE: Animal experiments have shown that the bladder-cooling reflex is activated by cold stimulation of the bladder and urethra, causing a reflex bladder contraction. In this clinical experimental study, the bladder reflex responses to distension and cooling of the bladder neck and the proximal urethra were investigated. MATERIAL AND METHODS: Twenty-one patients with overactive bladders and documented positive ice water tests were studied. RESULTS: Three patients (14%) responded with reflex bladder contraction by urethral infusion of ice water only, and another 4 patients responded to urethral distension with both warm and cold water. In 4 patients, bladder contraction was induced by a catheter pulling on the bladder neck. CONCLUSION: This study supports the existence of a cold-sensitive reflex system in the human urethra. However, in the experimental situation, both cold and tension-mediated reflexes were more difficult to evoke from the urethra than from the bladder.

Adolescent↗

Alterations in voiding frequency and cystometry in the clomipramine induced model of endogenous depression and reversal with fluoxetine.

PURPOSE: Because serotonin (5-HT) in the central nervous system may inhibit bladder activity, we postulated that depression associated with altered 5-HT function might be associated with overactive bladder (OAB). We examined a rat model of endogenous depression caused by lowering 5-HT for effects on voiding frequency (VF) and awake cystometry (CMG), and examined the effect of reversal using the selective serotonin reuptake inhibitor fluoxetine. MATERIALS AND METHODS: Wistar rat pups were divided into 2 groups, namely clomipramine treated (CL) and saline control (SC). From postnatal days 8 to 21 each pup was injected with CL hydrochloride (22.5 mg/kg body weight) or an equal volume of saline. VF was assessed at 10 and 15 weeks. Behavioral correlates of depression were assessed using the forced swim test. At age 15 weeks CMG was performed. Fluoxetine (20 mg/kg daily) was administrated to a subset of SC/CL rats, and VF and CMG were repeated. RESULTS: In CL rats immobility was increased when rats were submitted to the forced swim test, indicating depression. CL rats voided more frequently than the SC group at 10 and 15 weeks but the difference was significant only in females. CMG of female CL group showed decreased bladder capacity, micturition volume and intermicturition contractions compared with the SC group. Treatment with fluoxetine reversed these changes, as in SC rats. CONCLUSIONS: These results support the hypothesis that OAB in a subgroup of depressed individuals may be associated with altered 5-HT function. It may explain reports of an association between depression and OAB.

Animals↗

Botulinum toxin: poisoning the spastic bladder and urethra.

Botulinum toxin has proven to be a safe and effective therapy for a variety of somatic and autonomic motor disorders. Urologists are now finding clinical success with urethral and bladder injection of this fascinating toxin for detrusor sphincter dyssynergia, conditions of pelvic floor spasticity, and overactive bladder. One cannot deny the ingenuity of man in transforming the lethal toxin of Clostridium botulinum into a modern day therapeutic medicine.

Journal Article↗

The newer antimuscarinic drugs: bladder control with less dry mouth.

Two newer antimuscarinic anticholinergic drugs--tolterodine and extended-release oxybutynin--are approximately as effective in treating overactive bladder as immediate-release oxybutynin, but are more tolerable. I review clinical trial data on the newer agents.

Benzhydryl Compounds↗

Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor as urine markers for interstitial cystitis.

We previously determined that the urine of interstitial cystitis (IC) patients specifically contains a factor (antiproliferative factor [APF]) that inhibits primary bladder epithelial cell proliferation, and that it has significantly decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and increased levels of epidermal growth factor (EGF) compared with urine from asymptomatic controls and patients with bacterial cystitis. We sought to confirm the specificity of these findings for IC using a larger patient population, including control patients with a variety of urogenital disorders. Clean catch urine specimens were collected from 219 symptomatic IC patients, 113 asymptomatic controls without bladder disease, and 211 patients with various urogenital diseases including acute bacterial cystitis, vulvovaginitis, chronic nonbacterial prostatitis, overactive bladder, hematuria, stress incontinence, neurogenic bladder, benign prostatic hyperplasia, bladder or pelvic pain without voiding symptoms, bladder cancer, prostate cancer, or miscellaneous diagnoses including anatomic disorders. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and EGF levels were determined by enzyme-linked immunosorbent assay. APF activity was present significantly more often in IC than control urine specimens (P <0.005 for IC vs any control group; sensitivity = 94%, specificity = 95%, P <10(-82) for IC vs all controls). HB-EGF levels were also significantly lower and EGF levels significantly higher in IC urine than in specimens from controls (P <10(-84) and P <10(-36), respectively). These findings confirm the utility of APF, HB-EGF, and EGF as markers for IC. Understanding the reasons for altered levels of these markers may lead to understanding the pathogenesis of this disorder.

Adult↗

Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate.

1 We have systematically reviewed the presence, functional responses and regulation of alpha(1)-, alpha(2)- and beta-adrenoceptors in the bladder, urethra and prostate, with special emphasis on human tissues and receptor subtypes. 2 Alpha(1)-adrenoceptors are only poorly expressed and play a limited functional role in the detrusor. Alpha(1)-adrenoceptors, particularly their alpha(1A)-subtype, show a more pronounced expression and promote contraction of the bladder neck, urethra and prostate to enhance bladder outlet resistance, particularly in elderly men with enlarged prostates. Alpha(1)-adrenoceptor agonists are important in the treatment of symptoms of benign prostatic hyperplasia, but their beneficial effects may involve receptors within and outside the prostate. 3 Alpha(2)-adrenoceptors, mainly their alpha(2A)-subtype, are expressed in bladder, urethra and prostate. They mediate pre-junctional inhibition of neurotransmitter release and also a weak contractile effect in the urethra of some species, but not humans. Their overall post-junctional function in the lower urinary tract remains largely unclear. 4 Beta-adrenoceptors mediate relaxation of smooth muscle in the bladder, urethra and prostate. The available tools have limited the unequivocal identification of receptor subtypes at the protein and functional levels, but it appears that the beta(3)- and beta(2)-subtypes are important in the human bladder and urethra, respectively. Beta(3)-adrenoceptor agonists are promising drug candidates for the treatment of the overactive bladder. 5 We propose that the overall function of adrenoceptors in the lower urinary tract is to promote urinary continence. Further elucidation of the functional roles of their subtypes will help a better understanding of voiding dysfunction and its treatment.

Adrenergic Agonists↗

Effects of local anesthetics on the contractility of rat bladders.

PURPOSE: We investigated the effect of local anesthetic agents on the detrusor muscle in rats. MATERIALS AND METHODS: In vitro isometric contraction of rat detrusor strips was measured. We investigated the effects of tetracaine, bupivacaine and lidocaine on baseline spontaneous contractions and contractions induced by various stimuli, including 60 mM. KCl, carbachol and electricalal field stimulation with a pulse duration of 0.8 or 100 milliseconds. RESULTS: Local anesthetic agents have complex effects on baseline spontaneous contractility that depend on the type of agent used and its concentration. These agents inhibited nerve mediated contraction resulting from electricalal field stimulation with a pulse duration of 0.8 milliseconds in a concentration dependent manner and also inhibited nonnerve mediated detrusor contractions induced by KCl, carbachol or electricalal field stimulation with a pulse duration of 100 milliseconds Higher concentrations of local anesthetic agents were needed to inhibit nonnerve than nerve mediated contractions. In rat detrusor muscle carbachol induced a sustained tonic contraction even after the depletion of internal and external Ca2+ sources, which was also inhibited by local anesthetic agents. CONCLUSIONS: These results show that local anesthetic agents have a wide spectrum of inhibitory effects on the contraction of bladder smooth muscle induced by various stimulants at different concentrations, which may be potentially useful for treating overactive bladder.

Anesthetics, Local↗