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PubMed2002

Current and future pharmacological treatment for overactive bladder.

PURPOSE: Urinary incontinence and overactive bladder are important and common conditions that have received little general medical attention. We reviewed the magnitude and impact of these conditions, and discuss pharmacotherapy as well as new drugs under investigation. MATERIALS AND METHODS: The main emphasis of this review is pharmacological therapy for the bladder. We discuss currently available agents, drugs under development and pharmacological targets that would be suitable targets for treating overactive bladder. Drugs such as duloxetine that target not bladder smooth muscle, but rather central nervous system control of the micturition reflex are undergoing clinical trials. We also discuss intravesical therapy and alternative drug delivery methods, such as intravesical capsaicin and botulinum toxin, with special emphasis on approaches to modulate bladder afferent nerve function for preventing overactive bladder. RESULTS: There are many advantages to advanced drug delivery systems, including long-term therapeutic efficacy, decreased side effects and improved patient compliance. Future speculation such as gene therapy holds great promise for overactive bladder because it is possible to access all genitourinary organs via endoscopy and other minimally invasive techniques that are ideally suited for gene therapy. CONCLUSIONS: Traditional anticholinergic therapies are limited in their effectiveness. There is great hope for future research regarding voiding dysfunction and urinary incontinence through a focus on afferent nerve intervention for preventing overactive bladder.

Adult↗
PubMed1997

The overactive bladder: pharmacologic basis of drug treatment.

OBJECTIVES: To provide an overview of the basis for drug treatment of the overactive bladder. METHODS: Published information is evaluated. RESULTS: The causes of bladder overactivity are not known, but theoretically, increased afferent activity, decreased inhibitory control in the central nervous system (CNS) or peripheral ganglia, and increased sensitivity of the detrusor to efferent stimulation may be involved. Several CNS transmitters can modulate voiding, but few useful drugs with a defined CNS site of action have been developed. Drugs that stimulate gamma-aminobutyric acid receptors are used clinically. Potentially, drugs affecting opioid, 5-hydroxytryptamine, norepinephrine, dopamine, and glutamatergic receptors and mechanisms can be developed, but a selective action on the lower urinary tract may be difficult to obtain. Traditionally, drugs used for treatment of bladder overactivity have had a peripheral site of action, mainly efferent neurotransmission or the detrusor itself. Antimuscarinic drugs, beta-adrenoceptor agonists, alpha-adrenoceptor antagonists, drugs affecting membrane channels, prostaglandin synthetase inhibitors, and several other agents have been used with limited success. New information on the alpha-adrenoceptor and muscarinic receptor subtypes in the human detrusor has emerged and may be the basis for the development of new compounds with effects on bladder overactivity. Decreasing afferent activity seems an attractive therapeutic approach, and drugs affecting afferent nerves by causing release of tachykinins, such as capsaicin and analogs, as well as agents blocking tachykinin receptors, may be of therapeutic interest. CONCLUSIONS: New drugs, specifically designed for the treatment of bladder overactivity, are desirable.

Central Nervous System↗
PubMed2002

Prevalence and burden of overactive bladder in the United States.

CONTEXT: the National Overactive BLadder Evaluation (NOBLE) Program was initiated to better understand the prevalence and burden of overactive bladder in a broad spectrum of the United States population. OBJECTIVE: to estimate the prevalence of overactive bladder with and without urge incontinence in the US, assess variation in prevalence by sex and other factors, and measure individual burden. DESIGN: US national telephone survey using a clinically validated interview and a follow-up nested study comparing overactive bladder cases to sex- and age-matched controls. SETTING: noninstitutionalized US adult population. PARTICIPANTS: a sample of 5,204 adults >/=18 years of age and representative of the US population by sex, age, and geographical region. MAIN OUTCOME MEASURES: prevalence of overactive bladder with and without urge incontinence and risk factors for overactive bladder in the US. In the nested case-control study, SF-36, CES-D, and MOS sleep scores were used to assess impact. RESULTS: the overall prevalence of overactive bladder was similar between men (16.0%) and women (16.9%), but sex-specific prevalence differed substantially by severity of symptoms. In women, prevalence of urge incontinence increased with age from 2.0% to 19% with a marked increase after 44 years of age, and in men, increased with age from 0.3% to 8.9% with a marked increase after 64 years of age. Across all age groups, overactive bladder without urge incontinence was more common in men than in women. Overactive bladder with and without urge incontinence was associated with clinically and significantly lower SF-36 quality-of-life scores, higher CES-D depression scores, and poorer quality of sleep than matched controls. CONCLUSIONS: the NOBLE studies do not support the commonly held notion that women are considerably more likely than men to have urgency-related bladder control problems. The overall prevalence of overactive bladder does not differ by sex; however, the severity and nature of symptom expression does differ. Sex-specific anatomic differences may increase the probability that overactive bladder is expressed as urge incontinence among women compared with men. Nonetheless, overactive bladder, with and without incontinence, has a clinically significant impact on quality-of-life, quality-of-sleep, and mental health, in both men and women.

Adolescent↗
PubMed1998

Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder.

OBJECTIVE: To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (> or = micturitions/24 h) and symptoms of urgency and/or urge incontinence (> or = 1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition. RESULTS: After 12 weeks' treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n = 118) and oxybutynin (n = 118), respectively, and by 10.5% in those on placebo (n = 57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily. CONCLUSION: Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.

Adult↗
PubMed2002

State of the science: pathology and management of the patient with overactive bladder.

A relatively new term, overactive bladder is used to describe urinary frequency, urgency, and nocturia with or without urinary incontinence. Normal micturition involves coordination among the nervous system, the bladder, and the sphincter. Theories about pathogenesis include disorders of the central and peripheral nervous system, lowered levels of neurotransmitters, and structural problems of the bladder and sphincter. Assessing the patient with overactive bladder incorporates a thorough history and focused physical exam. Current treatments for this condition include lifestyle changes, behavioral interventions, pharmacologic management, and neuromodulation therapy. Research into different medications and delivery systems proves promising for the patient with overactive bladder.

Aged↗
PubMed2002

Special considerations in premenopausal and postmenopausal women with symptoms of overactive bladder.

The term overactive bladder (OAB) is used to describe the symptoms of urinary frequency and urgency with or without urge incontinence. Commonly reported symptoms are nocturia, urgency, frequency, and urge incontinence. However, some of these symptoms may be because of other lower urinary tract conditions or may simply represent a variant of normal physiologic function. Consequently, special considerations need to be made when diagnosing OAB in women. In women of all ages, lower urinary tract infection is the most common cause of irritative urinary symptoms, and midstream urine microscopy and culture should be performed. A chronic urinary residual secondary to voiding difficulties may also result in symptoms of frequency and overflow incontinence and may be diagnosed using a postmicturition ultrasound scan. In premenopausal women, pregnancy should also be excluded. In postmenopausal women, urogenital atrophy can cause irritative symptoms that may be improved with hormone replacement therapy. Vaginal administration has been shown to be most effective and may be used to supplement systemic replacement therapy. In addition, estrogen replacement may be beneficial in the management of OAB as an adjunct to anticholinergic therapy. When investigating elderly women with OAB, special consideration should be given to comorbidities, such as constipation and fecal impaction, mobility problems, and the loss of independence. Concomitant medication, such as diuretics and alpha-adrenergic blockers, should also be noted and the need for therapy reviewed. In conclusion, OAB is a subjective diagnosis that should only be made when other lower urinary tract conditions have been excluded.

Cholinergic Antagonists↗
PubMed2002

Once-daily, extended-release formulations of antimuscarinic agents in the treatment of overactive bladder: a review.

Overactive bladder (OAB) is a chronic condition that often requires long-term treatment to maintain control of symptoms. A range of therapeutic options are available; however, antimuscarinic agents form the mainstay of treatment. Of these agents, tolterodine and oxybutynin are the most widely used. It is well documented that the immediate-release (IR) formulations of these agents have equivalent efficacy in relieving OAB symptoms. However, tolterodine demonstrates a more favorable tolerability profile, particularly in terms of the frequency and severity of dry mouth. Due to the development of novel drug delivery systems, extended-release (ER) formulations of both oxybutynin and tolterodine are now available, permitting once-daily dosing. The convenience of once-daily dosing of antimuscarinic agents would be expected to improve patient compliance and further relieve the symptoms of OAB. Clinical studies with the ER formulations of tolterodine and oxybutynin demonstrate potential clinical advantages over their respective IR forms in terms of either efficacy or tolerability or both, although the therapeutic index of tolterodine ER appears to show a greater advantage over its IR counterpart compared with oxybutynin ER and its IR form. Importantly, the two ER agents have not been compared directly in a head-to-head clinical study. Overall, available clinical data suggest that the newly developed ER formulation of tolterodine represents a significant therapeutic advancement in the treatment of OAB.

Administration, Oral↗
PubMed2004

The wet patient: understanding patients with overactive bladder and incontinence.

Overactive bladder (OAB) is a constellation of lower urinary tract symptoms, including urinary frequency and urgency,which can occur with or without urinary incontinence. Incontinence is present in over half of female patients with OAB. This condition affects more than 33 million Americans and imposes considerable economic, social, and psychological burdens. Although continued improvements in the pharmacologic management of lower urinary tract disorders have led to the availability of well-tolerated, characteristic features, prevalence and epidemiology, effective treatment options, the symptoms of OAB are generally underreported by patients and under treated by healthcare professionals. Heightened awareness of the multifaceted disease burden imposed by OAB and increased understanding of the characteristics of patients who are likely to be most severely affected, in particular those who suffer from incontinence, may improve the timely identification, diagnosis, and clinical management of the syndrome, enhancing both the health and quality of life of these patients. This review will summarize the clinical consequences, and management of OAB, with particular focus on the incontinent patient.

Adult↗
PubMed2002

Conservative therapy for overactive bladder: pelvic floor exercises.

Overactive bladder affects the lives of millions of people. Anticholinergic medications are traditionally used to treat this condition, but some patients find these agents difficult to tolerate and ineffective. Conservative treatment with pelvic floor exercises, with or without biofeedback, electric stimulation, and behavioral modification, are excellent modalities that can be effective in the motivated patient. This review describes the available literature supporting the efficacy of pelvic floor exercises in the treatment of overactive bladder and guidelines for patient selection.

Electric Stimulation Therapy↗
PubMed2000

Lower urinary tract symptoms, benign prostatic obstruction and the overactive bladder.

Lower urinary tract symptoms (LUTS), benign prostatic obstruction (BPO), and the overactive bladder have increasing prevalence with age in both men and women (with the obvious exception). The question is, are they interrelated or independently related to age? The specific issue is whether BPO causes the overactive bladder. There are two pieces of evidence that might appear to suggest such a cause and effect. First, the overactive bladder is more common in men than in women of the same age, although physiologically, men are 5-10 years older at the same biological age. Second, the overactive bladder resolves in two-thirds of individuals after surgical interventions such as transurethral prostatectomy. The symptoms suggestive of an overactive bladder are the most troublesome, even though they may not be the most prevalent. Long-term follow-up studies with repeated urodynamic investigations have shown that the incidence of the overactive bladder and its attendant symptoms increases despite there being no deterioration in outlet obstruction over follow-up periods of 10 and 20 years. These data, and others, indicate that the situation is not as straightforward as some believe. The statement that 'the overactive bladder is secondary to BPO' cannot be made, as there are too many unanswered questions and pieces of the puzzle that do not fit. The overactive bladder is undoubtedly associated with BPO, and it leads to the most troublesome LUTS in older men. Epidemiological research, coupled with urodynamic evaluation, may provide further evidence. We also need better and more relevant models (e.g. ageing animals), together with further histological and other biological data before the waters become crystal clear.

Aging↗
PubMed2000

Intravesical neuromodulatory drugs: capsaicin and resiniferatoxin to treat the overactive bladder.

Current pharmacologic treatment of the overactive bladder relies on anticholinergic drugs. However, these drugs often have troublesome side effects and frequently are given in doses insufficient to restore continence in patients with detrusor instability. We present the background and basic and clinical research dealing with intravesical instillation of capsaicin and resinfferatoxin as treatments for the overactive bladder. Capsaicin is the main pungent ingredient in "hot" peppers of the genus Capsicum. It is a specific neurotoxin that desensitizes C-fiber afferent neurons, which may be responsible for the signals that trigger detrusor overactivity. Studies with capsaicin over the past 8 years have demonstrated clinical efficacy with minimal long-term complications. Most of these studies have also shown that the acute pain and irritation associated with capsaicin are a major deterrent to widespread use. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin that appears to have similar efficacy but with much less acute side effects may be more useful. Intravesical instillation of capsaicin or resiniferatoxin is a promising treatment for the overactive bladder.

Administration, Intravesical↗
PubMed1999

Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder.

PURPOSE: Pharmacological treatment of the overactive bladder relies on partially blocking the efferent parasympathetic innervation to the detrusor with anticholinergic drugs. However, often these drugs have troublesome side effects and doses are insufficient to restore continence in patients with detrusor instability. We present the background, basic and clinical research with intravesical instillation of capsaicin and resiniferatoxin as treatments for the overactive bladder. MATERIALS AND METHODS: Capsaicin, the main pungent ingredient in hot peppers of the genus Capsicum, is a specific neurotoxin that desensitizes C fiber afferent neurons which may be responsible for signals that trigger detrusor overactivity. RESULTS: In the last 6 years studies have demonstrated encouraging improvement in lower urinary tract symptoms with minimal long-term complications. Most of these studies have also demonstrated that the acute pain and irritation associated with capsaicin are major deterrents to widespread use. Therefore, resiniferatoxin, an ultra-potent analogue of capsaicin which appears to have similar efficacy but less acute side effects, may be more useful. CONCLUSIONS: Intravesical capsaicin and resiniferatoxin are novel and promising treatments for the overactive bladder, with profound basic and clinical implications.

Administration, Intravesical↗
PubMed2004

Retrospective analysis of efficacy and tolerability of tolterodine in children with overactive bladder.

OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine in children with an overactive bladder, treated in a single incontinence centre. MATERIALS AND METHODS: A retrospective analysis of a database of a total of two hundred and fifty-six patients (175 boys and 81 girls, age range 3 years to 17 years, mean age 8.33 years) with urodynamically confirmed bladder overactivity was performed. All children received tolterodine tartrate (dose range of 0.5-4 mg orally). In group I (n=205) tolterodine tartrate replaced anticholinergic drugs (AC) (oxybutinin chloride or oxyphencyclimin hydrochloride). A subgroup of patients switched because of intolerance due to serious adverse events (60.4%) or because of lack of improvement in micturition variables (39.6%). In group II tolterodine was prescribed as initial therapy (n=51). Tolerability was assessed by a standardised questionnaire on adverse events at every outdoor clinic visit. Efficacy assessment was based on micturition diary variables, mean change of maximum bladder capacity and number of incontinence episodes/24 h. RESULTS: The mean treatment time was 9.32 months with a range from 1.5 months to 23.4 months. The final dose was 0.1mg/kg orally daily divided into two doses. In group I central nervous system disorders (81%) were the most common adverse events, 26.2% showed flushing, 12.2% accommodation problems and 25.2% had gastrointestinal complaints (constipation, encopresis, abdominal pain). Withdrawal of the non-selective antimuscarinic drug resulted in total recovery from adverse events. Introduction of tolterodine in group I and II caused no serious adverse events. Nine patients (3.5%) reported side-effects and only two discontinued treatment. There were no reports of flushing, troubles of visual accommodation, hyperpyrexia. In group I we observed a mean decrease in urgency by 38.7%, a mean increase in maximal bladder capacity by 33.6% and the number of incontinence episodes decreased by 64.8%. In group II we observed equivalent values with a significant (p<0.001) change in maximal bladder capacity (49.7%), incontinence episodes (64.8%) and micturition episodes/24 h. CONCLUSIONS: The results of this retrospective analysis suggest that tolterodine is well tolerated in children and offers an effective treatment for urinary symptoms due to overactive bladder. Tolterodine is superior to non-selective antimuscarinic drugs, with respect to adverse events, allowing more compliance and more effective treatment in children.

Adolescent↗
PubMed2001

Expression of neural plasticity related gene in the pontine tegmental area of rats with overactive bladder after cerebral infarction.

PURPOSE: We investigated the expression of the neural plasticity related genes c-fos, zif268, c-jun, brain-derived neurotrophic factor and tissue plasminogen activator in the pontine tegmental area in rats with overactive bladder induced by cerebral infarction. MATERIALS AND METHODS: Cerebral infarction was induced by left middle cerebral artery occlusion in female Sprague-Dawley rats. Bladder activity was monitored by continuous infusion cystometrography in awake rats. Specimens were obtained from the pontine tegmental area 1, 3, 5, 12 and 24 hours after cerebral infarction or sham operation. The effect of 0.1 mg./kg. intravenously of the N-methyl-d-aspartate glutamatergic receptor antagonist MK-801 on bladder activity, and c-fos and zif268 expression after middle cerebral artery occlusion were studied. Real-time reverse transcriptase-polymerase chain reaction was performed with the LightCycler system (Roche Diagnostics, Mannheim, Germany) to evaluate cerebral infarction influences on gene expression in the pontine tegmental area. RESULTS: Bladder capacity in cerebral infarcted rats was significantly reduced 1 to 24 hours after middle cerebral artery occlusion compared with that of sham operated rats (p <0.05 to 0.01). One hour after occlusion mean c-fos messenger (m)RNA expression plus or minus standard error had significantly increased to 18.9 +/- 4.0 in terms of its density relative to the outer control in a sample obtained immediately after occlusion compared with that in sham operated rats (p <0.05). It returned to the control level within 3 hours after occlusion. Mean zif268 mRNA expression significantly increased to a relative density of 3.2 +/- 1.4 3 hours after middle cerebral artery occlusion (p <0.01) and returned to the control level within 5 hours after occlusion. The expressions of c-jun, brain-derived neurotrophic factor and tissue plasminogen activator was not influenced by occlusion. Pretreatment with MK-801 inhibited bladder overactivity and significantly reduced the expression of c-fos and zif268 mRNA in the pontine tegmental area. CONCLUSIONS: These results indicate that the development of bladder overactivity after middle cerebral artery occlusion is mediated by activation of an N-methyl-d-aspartate receptor and accompanied by an increase in c-fos and zif268 mRNA expression in the pontine tegmental area.

Animals↗
PubMed2003

[Diagnosis of overactive bladder influenced by methods of clinical assessment--micturition diary vs. urodynamics].

INTRODUCTION: Most characteristic symptom of overactive bladder is urgent, possibly painful, desire to void. This complaint is caused by autonomous bladder contractions. The increased activity of detrusor muscle is not only responsible for the urgency but also is the direct reason for the development of urge urinary incontinence. THE AIM OF THE STUDY: The comparison of the subjective (micturition diary) and objective (urodynamic investigation) mode of diagnosis of overactive bladder. MATERIAL AND METHOD: Twenty one women complaining of symptoms of the overactive bladder were included into the study. The infection of lower urinary tract was ruled out based on the results of urinalysis. Each patient reported urinary symptoms (number of urgency episodes and urge urinary leakages) in micturition diary for seven days. Thereafter, all participants underwent the urodynamic investigation that included uroflowmetry and cystometry. RESULTS: Data obtained from micturition diaries proved that all patients had subjective symptoms of overactive bladder (n = 21). However, only 8 subjects met overactive bladder diagnostic criteria on urodynamic investigation. The data obtained from micturition diaries and urodynamics were compared between group with objectively (urodynamic investigation) and subjectively (micturition diary) diagnosed overactive bladder. CONCLUSIONS: 1. There is marked discrepancy between data obtained from micturition diary and the results of urodynamic investigation. 2. It was shown that the diagnosis of overactive bladder cannot be made solely on the basis of maturation diary. 3. Volume of voided urine measured at uroflowmetry and volume of infused fluid causing strong desire to void are best markers of urodynamically proven diagnosis of overactive bladder.

Diagnosis, Differential↗
PubMed1998

Pharmacologic options for the overactive bladder.

OBJECTIVES: To review the current pharmacologic options for treatment of the overactive bladder and to describe potential therapies on the horizon. METHODS: The literature on the clinical efficacy and safety of the currently available agents is described. RESULTS: According to the guidelines issued by the Agency for Health Care Policy and Research (AHCPR), anticholinergic agents should be the first-line pharmacologic therapy for patients with detrusor instability. Oxybutynin is the anticholinergic of choice for this indication, whereas propantheline is the second-line therapy. Although calcium antagonists have been investigated, the one such drug introduced for the treatment of overactive bladder (terodiline) was withdrawn from the market because of a risk of cardiac arrhythmia. Studies of potassium channel openers have found either a lack of clinical efficacy or an unacceptable level of side effects. Alpha-adrenergic antagonists may be useful for decreasing bladder overactivity in patients who have autonomous bladders as the result of conditions such as spinal cord injury. Tricyclic antidepressants (particularly imipramine) may be effective in decreasing bladder contractility, although the AHCPR guidelines caution that these drugs should be reserved for use in carefully evaluated patients. Future developments in the treatment of detrusor overactivity are likely to occur in 3 categories: drugs that affect peripheral excitatory mechanisms, drugs that inhibit afferent mechanisms, and drugs that affect more central actions at either the ganglionic, spinal cord, or supraspinal level. CONCLUSIONS: Although pharmacologic management of the overactive bladder has progressed little in the past 10 years, the future may hold the promise of more effective therapies.

Antidepressive Agents, Tricyclic↗
PubMed2003

RNA synthesis in pons necessary for maintenance of bladder overactivity after cerebral infarction in rat.

PURPOSE: The maintenance of long lasting bladder overactivity caused by cerebral infarction is believed to require transcription in the pontine micturition center. Therefore, we examined the influence of the RNA synthesis inhibitor actinomycin D (Banyu Pharmaceutical Co., Ltd., Tokyo, Japan) on bladder overactivity induced by left middle cerebral artery occlusion. MATERIALS AND METHODS: Rats under halothane anesthesia were injected with actinomycin D or vehicle (mannitol) into the bilateral dorsal pontine tegmentum, followed by middle cerebral artery occlusion. Awake rats were cystometrically examined for 12 hours. The expression of c-fos and zif268 mRNA in the dorsal pontine tegmentum was monitored with real-time polymerase chain reaction. RESULTS: Injection of actinomycin D produced a significant decrease in bladder capacity in sham operated rats but bladder capacity returned to control levels before sham operation within 6 hours. In cerebral infarcted rats pretreated with vehicle bladder capacity was significantly decreased after middle cerebral artery occlusion and it remained consistently below half of pre-occlusion capacity. Actinomycin D blocked the decrease in bladder capacity in cerebral infarcted rats. In actinomycin D treated cerebral infarcted rats bladder capacity gradually recovered and returned to the control level before middle cerebral artery occlusion within 10 hours. Actinomycin D suppressed an increase in c-fos mRNA expression 1 hour after middle cerebral artery occlusion as well as in zif268 3 hours after occlusion. Administering actinomycin D 0.5 or 1 hour after middle cerebral artery occlusion also suppressed bladder overactivity until at least 10 hours after occlusion but injection 3 hours after occlusion did not. CONCLUSIONS: These results indicate that an RNA synthesis inhibitor can prevent a late stage of bladder overactivity. Transcription in the dorsal pontine tegmentum was found to be necessary to maintain the long lasting bladder overactivity caused by cerebral infarction.

Animals↗