Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677481 (urinary frequency)
 1,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxybutynin possesses anticholinergic and spasmolytic properties, which together form the basis for its use as a therapeutic option in patients with overactive detrusor function--either idiopathic detrusor instability (DI) or detrusor hyperreflexia. Of the symptoms of detrusor overactivity, urge incontinence is often the most distressing to the patient. Urge incontinence and other subjective parameters (urinary frequency, urgency) improve in tandem with objective (cystometric) measures (maximum detrusor pressure during filling, volume at first desire to void, maximum bladder capacity) in ambulatory, including elderly, patients treated with oxybutynin. However, on the basis of results of limited investigations, the drug appears ineffective in elderly institutionalised individuals. Relative to other anticholinergic drugs, oxybutynin appears at least as effective as propantheline and similar in efficacy to propiverine in small trials, although these results are not definitive. Further investigation of intravesical oxybutynin may lead to this route becoming an option in patients with pre-existing catheters. Adverse effects--dry mouth, constipation, blurred vision--related to the anticholinergic activity of oxybutynin occur frequently and can be sufficiently troublesome to necessitate treatment discontinuation in up to 25% of patients, depending on the dosage. Increases in residual urine volume suggesting urinary retention (undesirable in patients with idiopathic DI), also can develop in some oxybutynin recipients. In summary, oxybutynin is one of the few drugs proven to be beneficial in some patients with overactive detrusor function. Despite the occurrence of unwanted anticholinergic effects in many patients, and apparent lack of efficacy in the elderly institutionalised population, oxybutynin should be considered for the drug of first choice in patients with detrusor overactivity, including the elderly ambulatory population, when pharmacological therapy is indicated.
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PMID:Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. 762 Feb 36

NS-21 ((+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) is a novel compound designed for the treatment of bladder dysfunction. The effects of NS-21 and its active metabolite, RCC-36 ((+/-)-4-ethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride), on the urodynamics of decerebrated dogs are reported. Dogs were decerebrated at the precollicular-postmamillary level and the urodynamic effects of intravenously administered NS-21, RCC-36, and various reference drugs were compared by cystometry. NS-21 (0.3-1 mg/kg) and RCC-36 (0.1 mg/kg) caused an increase in bladder capacity without affecting the micturition pressure or residual volume, and thus caused a significant increase in functional bladder capacity. Oxybutynin caused a dose-dependent increase in bladder capacity at 0.1 mg/ kg and higher doses; however, the associated decrease in micturition pressure resulted in a significant increase in residual volume and a decrease in functional bladder capacity. These effects of oxybutynin were similar to those of atropine. Propiverine (0.1-10 mg/kg) and terodiline (0.1-10 mg/kg) caused no significant increase in bladder capacity. In conclusion, in decerebrated dogs, NS-21 and RCC-36 increased the bladder capacity without increasing the residual volume. NS-21 thus had more favorable therapeutic effects than any of the reference drugs tested and is therefore a promising candidate drug for the treatment of pollakiuria and urinary incontinence.
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PMID:Effect of the anticholinergic drug with calcium antagonistic activity, (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, on lower urinary tract function in decerebrated dogs. 907 38

NS-21 ((+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) and its active metabolite, RCC-36 ((+/-)-4-ethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride), have both anticholinergic and calcium antagonistic activities. NS-21 is under development for the treatment of bladder dysfunction. This study was designed to compare the effects of NS-21 and RCC-36 on the bladder function of monkeys with the effects of various reference drugs. Male rhesus monkeys were anesthetized with a mixture of enflurane and nitrous oxide, a transurethral catheter was inserted into the urinary bladder from the external urethral orifice, and cystometrograms were recorded. Drugs were administered intravenously. NS-21 at doses of 0.3 and 1 mg/kg caused an increase in bladder capacity without affecting the micturition pressure. RCC-36 also caused an increase in bladder capacity, but it was accompanied by a significant decrease in micturition pressure. Oxybutynin, atropine and verapamil all caused decreases in micturition pressure at doses which caused an increase in bladder capacity. Of the drugs examined, only NS-21 caused an increase in the bladder capacity of rhesus monkeys without affecting the micturition pressure. This drug is therefore a promising candidate for the clinical treatment of pollakiuria and urinary incontinence.
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PMID:Effect of the anticholinergic drug with calcium antagonistic activity, (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, on lower urinary tract function in rhesus monkeys. 907 39

Propiverine is a drug for the treatment of incontinence and pollakiuria. Such micturitional disorders are principally caused by a hyperactive bladder. The effects of propiverine, its active metabolite, 1-methyl-4-piperidyl benzilate N-oxide (DPr-P-4 (N-->O)), oxybutynin and terodiline on muscarinic receptors in guinea pig urinary bladder, salivary glands, cerebral cortex, ileal longitudinal muscle and heart were compared. Both propiverine and DPr-P-4 (N-->O) competitively inhibited specific binding of 3H-quinuclidinyl benzilate (3H-QNB) to membrane fractions of these tissues. Oxybutynin, terodiline, pirenzepine and atropine also competitively inhibited the binding of 3H-QNB. The order of these drugs in terms of their affinity for muscarinic receptors was as follows: atropine > oxybutynin > pirenzepine, DPr-P-4 (N-->O), terodiline > propiverine. Propiverine and DPr-P-4 (N-->O) had no selectivity for muscarinic receptors in these tissues, the same as atropine. In contrast, pirenzepine, a M1-selective drug, had 10.1 times greater affinity for muscarinic receptors in the cerebral cortex than in urinary bladder, and the affinity of oxybutynin for muscarinic receptors in salivary glands and in cerebral cortex was 10.9 times and 13.9 times higher, respectively, than in urinary bladder. The affinity of terodiline for muscarinic receptors in the cerebral cortex was 4.4 times higher than in urinary bladder. In this study, the effect of propiverine and oxybutynin on pilocarpine (1 mg/kg, s.c.)-induced salivation in conscious dogs was also compared. Propiverine (5 mg/kg, i.v.) had no effect on pilocarpine-induced salivation, whereas oxybutynin (0.1 mg-0.5 mg/kg, i.v.) inhibited it significantly and dose-dependently. The ID50 values (95% confidence limits) for propiverine and oxybutynin during the 20 min after intravenous administration were 6.88 mg/kg (4.71-15.67) and 0.154 mg/kg (0.115-0.205), respectively. These findings suggest that although propiverine, its active metabolite DPr-P-4 (N-->O), oxybutynin and terodiline competitively inhibit the binding of 3H-QNB to muscarinic receptors, the affinity of these drugs for the muscarinic receptors of these tissues is very different and that propiverine has less effect on salivation than oxybutynin.
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PMID:[Effects of propiverine hydrochloride (propiverine) on the muscarinic receptor binding affinity in guinea pig tissues and on salivation in conscious dogs]. 1034 40

The effects of TAK-637 ((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8, 9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2 , 1-g][1,7]naphthyridine-6,13-dione), a novel tachykinin NK(1) receptor antagonist, on the micturition reflex in guinea pigs were studied in comparison with those of anti-pollakiuria agents. Cystometry was performed under urethane anesthesia. TAK-637 increased the volume threshold with a minimum effective dose of 0.03 mg/kg, i.v. without affecting voiding pressure. Oxybutynin, tolterodine, propiverine and inaperisone also increased the volume threshold in urethane-anesthetized guinea pigs, but they decreased voiding pressure, although the effect of propiverine was not statistically significant. A structurally unique tachykinin NK(1) receptor antagonist, (+/-)-CP-99,994 ((+/-)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), increased the volume threshold with a minimum effective dose of 0.3 mg/kg, i.v. TAK-637 increased the volume threshold with a minimum effective dose of 0.01 mg/kg, p.o. in unanesthetized guinea pigs. These results indicate that TAK-637 may be useful as pharmacotherapy for detrusor overactivity without decreasing voiding pressure or causing voiding difficulties.
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PMID:Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig. 1059 23

We investigated the effects of AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl] pyrrolidine fumarate; a novel sigma receptor ligand), (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG) (two typical sigma receptor ligands), and oxybutynin (a currently used anti-pollakiuria drug) on cystometrograms in anesthetized rats with 30% acetone-induced cystitis. Compared to sham-treated rats, acetone-treated cystitis models exhibited an increase in urinary frequency during continuous filling cystometry. Intravenous administration of AH-9700 (1-5 mg/kg), (+)-pentazocine or DTG to the rats with cystitis dose-dependently prolonged micturition intervals and increased the micturition threshold pressure. Oxybutynin (1 mg/kg. i.v.) also extended micturition intervals, but decreased the micturition pressure. These results indicate that AH-9700, (+)-pentazocine and DTG improve abnormal frequent urination caused by acetone-induced cystitis in a manner different from that of oxybutynin.
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PMID:Effects of AH-9700, (+)-pentazocine, DTG and oxybutynin on micturition in anesthetized rats with acetone-induced cystitis. 1158 9

The safety and efficacy of oxybutynin transdermal delivery system (oxybutynin-TDS) versus placebo in adults with urge and mixed urinary incontinence was investigated using combined results from double-blind stages of 2 phase 3 clinical trials. Study 1: placebo-controlled, parallel-group comparison of 3 oxybutynin-TDS doses in 12-week double-blind and open-label periods, followed by a 28-week open-label extension. Study 2 was a 12-week randomized, double-blind, placebo-controlled comparison of oxybutynin-TDS versus long-acting tolterodine and placebo, followed by a 52-week open-label extension. Efficacy analysis included 241 patients receiving oxybutynin-TDS, 244 receiving placebo. Most participants were Caucasian women (92%). Approximately 60% received prior anticholinergic therapy. Primary outcome was determined by changes from baseline to end of treatment in frequency of incontinence episodes, frequency of urination, and void volume. Oxybutynin-TDS was significantly more effective than placebo in reducing median daily incontinence episodes (-3.0 vs placebo -2.0; P=.00004) and daily urinary frequency (-2.0 vs -1.0; P=.0023), and in increasing void volume (25 mL vs 5.5 mL; P<.00001). Overall rates of anticholinergic adverse events (AEs) were 12.8% for oxybutynin-TDS and 11.0% for placebo (P=0.5421). The most common systemic anticholinergic AEs were dry mouth (7.0% for oxybutynin-TDS vs 5.3% for placebo) and constipation (2.1% vs 2.0%). Application site erythema occurred in 7.0% of participants who received oxybutynin-TDS (3.7% discontinuation rate); pruritus occurred in 16.1% (3.3% discontinuation rate). Transdermal oxybutynin was shown to be efficacious, with a proven safety profile. It may be utilized for patients with overactive bladder as a treatment option that could enhance compliance.
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PMID:Transdermal oxybutynin in the treatment of adults with overactive bladder: combined results of two randomized clinical trials. 1615 16

Overactive bladder (OAB) is a common condition characterised by the symptoms of urinary frequency and urgency, with or without urge incontinence and nocturia. The prevalence of OAB increases markedly with age in both men and women. OAB can have a detrimental effect on physical functioning and psychological well-being, as well as significantly reducing quality of life. Antimuscarinic therapy -- with or without behavioural therapy -- represents the most common treatment for patients with OAB. Several antimuscarinic agents are currently available for the treatment of OAB in adults, including oxybutynin, tolterodine, trospium chloride, darifenacin and solifenacin. The antimuscarinics all appear to exert their clinical effect through inhibition of the bladder muscarinic receptors, but they vary both in structure and in their functional profile. While efficacy has been demonstrated in adult populations (including patients >65 years of age), few studies have been reported specifically in a geriatric population, and antimuscarinics are often underutilised in the elderly despite the marked increase in the prevalence of OAB in this age group. One explanation for this apparent underuse of an effective treatment option may be concerns about the frequency of anticholinergic adverse events, such as dry mouth; the likelihood of detrimental CNS effects, including cognitive impairment and sleep disturbances; and the potential for harmful interactions with existing pharmacotherapy. When selecting an antimuscarinic agent for the management of an elderly patient presenting with OAB, in addition to considering evidence of clinical efficacy and tolerability, issues of safety specific to an older population should be borne in mind. In particular, the likelihood of detrimental CNS effects should be considered, including cognitive impairment and sleep disturbances, secondary to anticholinergic load. Oxybutynin and tolterodine have both been associated with cognitive adverse events and effects on sleep architecture and quality. In contrast, trospium chloride and darifenacin do not appear to be associated with cognitive adverse events and trospium chloride does not negatively affect sleep architecture or quality. Biotransformation by the cytochrome P450 (CYP450) system is an important step in the activation or elimination of a large number of drugs, including oxybutynin, tolterodine, darifenacin and solifenacin, raising the possibility of clinically relevant and potentially serious drug interactions. In elderly patients, such interactions are of particular relevance given the potential for declining activity of certain members of the CYP450 family combined with decreased hepatic blood flow, which can reduce first-pass metabolism and thus the bioavailability of drugs metabolised via this route. Of the antimuscarinic agents used to treat OAB, only trospium chloride is not extensively metabolised in the liver by the CYP450 system and is excreted largely as the active parent compound in the urine. This paper provides an overview of the pathophysiology of OAB and reviews current approaches to achieving a differential diagnosis and selecting appropriate treatment for the older patient. The pharmacology and clinical effects of current medication for the treatment of OAB symptoms in patients defined by the OAB pharmacology literature as 'elderly' are also reviewed.
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PMID:Overactive bladder in the elderly: a guide to pharmacological management. 1636 85

Oxybutynin has been used for the management of detrusor overactivity for over 30 years and has withstood medical scrutiny and the test of time throughout the world. Although several agents in the class of bladder relaxants have only recently been studied, oxybutynin's effectiveness in reducing urinary frequency and urge urinary incontinence is unquestioned in the medical literature. Oxybutynin is extremely safe and effective in almost every population including children, the elderly, and those who have neurogenic bladder. With more preparations available and more dosing flexibility than any other anticholinergic medication on the market, oxybutynin remains the "gold standard" for first-line therapy for patients who have detrusor overactivity.
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PMID:Oxybutynin in detrusor overactivity. 1701 79