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Kadekawa K.,Southern Knights Laboratory LLP | Nishijima S.,Southern Knights Laboratory LLP | Ashitomi K.,Southern Knights Laboratory LLP | Yamamoto H.,University of Ryukyus | Sugaya K.,Southern Knights Laboratory LLP
International Journal of Urology | Year: 2012

Objectives: To investigate the effects of the antimuscarinic agent, propiverine, on the bladder and urethra in rats. Methods: A total of 54 female rats were given propiverine, imidafenacin (an antimuscarinic agent), or distilled water by gavage once or twice daily. After 2weeks, bladder and urethral activity were recorded under urethane anesthesia. In the propiverine group, the changes of bladder and urethral activity before and after intravenous injection of α 1-adrenergic antagonists (prazosin, silodosin and naftopidil) were also recorded. Furthermore, the leak point pressure after electrical stimulation of abdominal wall muscles was measured in rats with vaginal distension from the control and propiverine groups. Results: Intravesical baseline pressure was significantly lower in the propiverine and imidafenacin groups compared with the control group, whereas the urethral baseline pressure was significantly higher in the propiverine group compared with the control or imidafenacin groups. Intravenous injection of prazosin (an α 1-receptor antagonist) significantly decreased the urethral baseline pressure in both of the propiverine and control groups. Intravenous injection of silodosin and naftopidil (α 1A- and α 1D-receptor antagonists, respectively) significantly decreased the maximum contraction pressure and the urethral baseline pressure in the propiverine group. The leak point pressure of the propiverine group was significantly higher than that of the control group. Conclusions: An increase of catecholamines after propiverine administration might activate smooth muscle of the proximal urethra via α 1A- and α 1D-adrenergic receptors, as well as activating urethral and pelvic floor striated muscle via the spinal motoneurons. © 2012 The Japanese Urological Association. Source

Nishijima S.,Southern Knights Laboratory LLP | Sugaya K.,Southern Knights Laboratory LLP | Kadekawa K.,Southern Knights Laboratory LLP | Ashitomi K.,Southern Knights Laboratory LLP | Yamamoto H.,University of Ryukyus
Life Sciences | Year: 2011

Aims: We examined the influence of propiverine hydrochloride, an anticholinergic agent, on the micturition reflex, blood pressure, and plasma catecholamine levels in young rats and old rats. Main method: Male F344/DuCrlCrlj Fischer rats (young rats aged 2 months and old rats aged 26 months) were divided into the following 4 groups: a young sham group, an old sham group, a young propiverine group, and an old propiverine group. Rats from the young (body weight: 215 ± 7 g) or old propiverine groups (body weight: 414 ± 22 g) were administered propiverine hydrochloride (5 or 10 mg, respectively) dissolved in distilled water (0.5 mL) into the stomach through a fine catheter once daily. Rats from the young and old sham groups were administered the same volume of distilled water. After 2 weeks of treatment, continuous cystometry was done with physiological saline and 0.1% acetic acid, and measurement of plasma catecholamines, blood pressure, and heart rate was performed. Key findings: The old rats had a longer interval between bladder contractions and higher plasma catecholamine levels than the young rats. Bladder stimulation by 0.1% acetic acid induced frequency in both young and old rats. Administration of propiverine inhibited the induction of frequency in the old rats, but not in the young rats. Propiverine increased plasma catecholamine levels in the young rats, but not in the old rats. Significance: These findings show that bladder activity varies with aging, and the response to propiverine also changes in an age-related manner. © 2011 Elsevier Inc. All rights reserved. Source

Sugaya K.,Kitakami Central Hospital | Sugaya K.,Southern Knights Laboratory LLP | Sekiguchi Y.,Yokohama Motomachi Womens Clinic LUNA | Satoh T.,Satoh Continence Clinic | And 4 more authors.
International Journal of Urology | Year: 2014

Objectives: To investigate whether the anticholinergic agent, propiverine hydrochloride, is clinically effective for stress urinary incontinence. Methods: The participants were adult female patients with the chief complaint of stress incontinence. Propiverine (20 mg once daily) was given for 8 weeks. If the response was inadequate after 4 weeks of treatment, the dose was increased to 40 mg/day. Before and after 4 and 8 weeks of treatment, lower urinary tract symptoms were assessed. The urethral pressure and blood catecholamine levels were also measured. Results: A total of 37 patients (mean age 69 ± 11 years) were enrolled, including 15 patients with stress incontinence and 22 with mixed incontinence. The number of episodes of stress incontinence decreased significantly from 2.6 ± 2.3 times per day to 1.3 ± 2.2 times per day after 4 weeks, and 0.4 ± 0.6 times per day after 8 weeks. The daytime and night-time frequency of urination, and quality of life score showed significant improvement. The maximum urethral closing pressure and the functional urethral length increased significantly after treatment, but blood catecholamine levels, blood pressure and pulse rate at 8 weeks were not significantly different from those at baseline. Conclusions: Propiverine could be an effective drug for stress urinary incontinence by increasing urethral closing pressure without increasing blood catecholamine levels. © 2014 The Japanese Urological Association. Source

Sugaya K.,Southern Knights Laboratory LLP | Kadekawa K.,Southern Knights Laboratory LLP | Onaga T.,Okinazva Kyodo Hospital | Ashitomi K.,Southern Knights Laboratory LLP | And 8 more authors.
Japanese Journal of Urology | Year: 2014

(Purpose) Since distigmine can cause the serious side effect of cholinergic crisis, its dosage regimen has been reduced to 5 mg/day for patients with difficulty in urination due to detrusor underactivity. Therefore, the efficacy and safety of add-on therapy with distigmine at 5 mg daily were examined in patients with persistent urination problems due to detrusor underactivity despite administration of α1-blockers. (Patients and methods) The subjects were 39 patients with underactive bladder (18 men and 21 women with an average age of 75 years) who showed no improvement of difficulty in urination or had a residual urine volume ≥ 50 ml despite the administration of α1-blockers for more than 4 weeks. They received treatment with distigmine (5 mg daily after breakfast) in addition to their α1-blockers for 8 weeks. The international prostate symptom score (IPSS), qualityof-life (QOL) score, residual urine volume, blood pressure, and biochemistry tests were investigated before and after addition of distigmine. (Results) After four and eight weeks of distigmine administration, all items of the IPSS and QOL score, as well as the residual urine volume, showed a significant decrease. In contrast, the pressure and pulse rate were unchanged. Serum creatinine showed a slight but significant decreased. As adverse events, frequent defecation, fecal incontinence, diarrhea, frequent urination and poor physical condition were recognized in 4 patients, but there was no serious event. (Conclusion) For difficulty in urination due to detrusor underactivity, the combination of an cd-blocker with distigmine at 5 mg daily showed early efficacy and good safety. © 2014 The Japanese Urological Association. Source

Kadekawa K.,Southern Knights Laboratory LLP | Onaga T.,Okinawa Kyodo Hospital | Shimabukuro S.,Tomishiro Central Hospital | Shimabukuro H.,Tomishiro Central Hospital | And 4 more authors.
LUTS: Lower Urinary Tract Symptoms | Year: 2012

Objectives: Clinical efficacy, influence on quality of life (QOL), and safety of imidafenacin before sleeping were assessed in patients with overactive bladder (OAB) who suffered from nocturia. Methods: A total of 60 OAB patients with a mean age of 74 years (45 men and 15 women) who mainly complained of nocturia were enrolled. Imidafenacin (0.1 mg) was administered once daily before sleeping for four weeks. Then the patients were divided into two groups, "a stable-dose group" with sufficient efficacy who remained on 0.1 mg of imidafenacin daily, and "a dose-escalation group" with insufficient efficacy in whom the daily dose of imidafenacin was increased to 0.2 mg before sleeping. Lower urinary tract symptoms and postvoid residual volume (PVR) were examined before treatment and after 4 and 8 weeks of imidafenacin therapy. Results: In the stable-dose group, nighttime frequency decreased significantly from 3.4 ± 1.1 to 2.3 ± 1.1 and 2.6 ± 2.0 times after four and eight weeks, respectively. In the dose-escalation group, nighttime frequency did not change significantly (from 3.8 ± 1.5 to 3.6 ± 1.8 times) at four weeks, but decreased significantly to 2.8 ± 1.4 times at eight weeks. Daytime frequency, OAB symptom score, and IPSS-QOL index score were significantly improved in both groups at four and/or eight weeks. There was no increase of PVR and no serious adverse events. Conclusion: Administration of imidafenacin at 0.1-0.2 mg once daily before sleeping was safe and effective for the treatment of OAB with the main symptom of nocturia. © 2012 Wiley Publishing Asia Pty Ltd. Source

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