piperidines and Urinary-Incontinence

To investigate the safety and efficacy of litoxetine, a serotonin reuptake inhibitor, in treating urinary incontinence (UI) and mixed urinary incontinence (MUI).. Two randomized, double-blind, placebo-controlled clinical trials (RCT1 and RCT2) were conducted. RCT1, which included 196 women aged 18-75 with MUI randomized 1:1:1:1 to receive 10, 20, or 40 mg litoxetine or placebo orally twice daily (BID) for 12 weeks, investigated the efficacy (including changes in patient reported outcomes) and safety of litoxetine compared to placebo. RCT2, which included 82 men and women aged 18-70 with any UI type randomly assigned 2:1 to receive 30 mg litoxetine or placebo orally BID for 8 weeks including a 2 week dose titration period, investigated the safety (including psychiatric safety) and efficacy of litoxetine compared to placebo. Efficacy was measured as the change in number of incontinence episodes per week and assessed using an analysis of covariance with missing data imputed by Predictive Mean Matching. Safety was assessed by adverse events (AEs) and physical examinations and analyzed using descriptive statistics.. The 30-mg and placebo groups in RCT2 showed no difference in frequency of AEs, and litoxetine reduced the number of incontinence episodes per week compared to placebo. Although RCT1 suffered an unexpectedly high placebo response, and therefore did not meet the primary efficacy endpoint, 71% of participants receiving 40 mg litoxetine reported a clinically meaningful improvement in the King's Health Questionnaire.. Litoxetine may be a safe, effective and well-tolerated treatment for patients with UI.

Topics: Double-Blind Method; Female; Humans; Male; Piperidines; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Urge

Mixed mood states in bipolar disorder are difficult to treat and when present indicate worse illness trajectories. Several medications are US Food and Drug Administration approved to treat mixed episodes; however, the clinical trials have been short term and rarely reported depression response.. We conducted a 5-month open-label trial examining the tolerability and efficacy of iloperidone for bipolar disorder mixed episodes.. Mania and depression scores significantly improved over the course of the study for study completers (ie, 60%-68% improvement for manic symptoms and 41%-49% for depression symptoms). Improvements were observed early in the trial and after adjusting for concomitant medication effects. The average daily dose in completers was 15 mg. Thirty-nine percent (12/31) of the eligible sample discontinued early because of adverse effects. The adverse events most commonly associated with withdrawal were increased heart rate/palpitations (n = 5 of 12) and urinary incontinence/intense urge to urinate (n = 3 of 12).. In a subset of patients, iloperidone provides relief for classic manic, depression, and irritability symptoms associated with mixed episodes in a long-term trial. Adverse effect profiles are likely to be a major factor contributing to individualized medication use.

Topics: Adult; Antipsychotic Agents; Arrhythmias, Cardiac; Bipolar Disorder; Female; Humans; Isoxazoles; Male; Piperidines; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Urge; Young Adult

Donepezil hydrochloride, a central cholinergic drug, is widely used for improving cognitive decline in Alzheimer's disease (AD). We investigated whether donepezil might affect the lower urinary tract (LUT) function in AD.. Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) (0-70, increase as impairment), urinary questionnaire, and electromyography (EMG)-cystometry were performed in eight patients with AD before and after treatment with 5 mg/day of donepezil.. The first assessment (before donepezil) showed moderate cognitive decline in the patients as a mean ADAS-cog score of 27.0 (range: 17-35) (normal < 15). Seven patients had urinary symptoms including urinary urgency incontinence in five. EMG-cystometry revealed neurogenic detrusor overactivity in seven with a mean detrusor pressure of 44.9 cm H(2)O (20-101), mean bladder capacity of 202 ml (20-412), and post-void residuals in none. The second assessment (3 months after donepezil) showed a decrease in the ADAS-cog score to 23.3 (11-35) though without statistical significance. Urinary incontinence disappeared in one and none had a new onset of incontinence. EMG-cystometry revealed an increase in the detrusor pressure on overactivity to 54.1 cm H(2)O (20-122), but also an increase in the bladder capacity to 234 ml (80-400), and post-void residuals in one (40 ml).. Although the number of our patients was small, it seems possibly that donepezil could ameliorate cognitive function without serious adverse effects on the LUT function in patients with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Donepezil; Electromyography; Female; Humans; Indans; Male; Muscle Hypertonia; Nootropic Agents; Pilot Projects; Piperidines; Treatment Outcome; Urinary Incontinence; Urodynamics

To compare spectral analysis of the electrocardiogram (ECG) with mean arterial pressure (MAP) and heart rate (HR) monitoring in the detection of autonomic hyperreflexia (AHR) induced by sacral root stimulation.. Ten spinal cord injured patients scheduled for implantation of a sacral root stimulator for bladder retention were included. Under target controlled anesthesia with propofol 4 micro g*mL(-1) and remifentanil 4 ng*mL(-1), the patients were placed in the knee chest position. The sacral roots were exposed by laminectomy (L2-S1) and their function assessed by electrostimulation under urodynamic and cardiovascular monitoring. Online power spectrum densities were calculated from the ECG R-R interval by the MemCalc(TM) software using the maximum entropy method. Low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4 Hz) spectra were associated with sympathetic and parasympathetic activities respectively. The most extreme value of each variable was noted before and during each stimulation. A difference ( triangle up ) of more than 10% signified AHR. The comparison ( triangle up LF vs triangle up MAP and triangle up HF vs triangle up HR) was done by a concordance test with a kappa coefficient (k): -1 = total discordance to 1 = total concordance.. AHR was detected in six patients as an increase in LF and MAP (n = 4); an increase in LF, HF, MAP with a decrease in HR (n = 2). The detection delay was 5.3 +/- 1 sec (LF, HF) and 10.4 +/- 1.2 sec (MAP and HR). Concordance was 85% (LF vs MAP: k = 0.7) and 90% (HF vs HR: k = 0.8).. AHR induced by sacral root stimulation is detected by spectral analysis of the ECG earlier than MAP and HR. Other studies are needed to confirm these results.

Topics: Adolescent; Adult; Anesthetics, Intravenous; Autonomic Dysreflexia; Blood Pressure; Electric Stimulation; Electrocardiography; Female; Heart Rate; Humans; Laminectomy; Male; Middle Aged; Monitoring, Intraoperative; Piperidines; Propofol; Reflex, Abnormal; Remifentanil; Spinal Cord Injuries; Spinal Nerve Roots; Urinary Incontinence; Urodynamics

Topics: Acetaminophen; Aged; Aged, 80 and over; Automobile Driving; Cognition Disorders; Cognitive Dysfunction; Colonic Neoplasms; Delirium; Dementia; Donepezil; Early Detection of Cancer; Estrogen Replacement Therapy; Female; Geriatrics; Humans; Indans; Male; Neuropsychological Tests; Nootropic Agents; Oxycodone; Piperidines; Urinary Incontinence; Watchful Waiting

Remifentanil, an ultrarapid-acting opioid, as an intravenous infusion, generally in combination with a sedative/amnesic (for example midazolam) and local anaesthesia can provide an effective assisted local anaesthetic technique (Remi-ALA) for tension-free vaginal tapes or equivalent continence procedures in urogynaecology. Excellent analgesia for the local anaesthetic injections and tape insertion is provided as well as optimal patient cooperation for clinicians who wish to perform cough testing after tape insertion. Dose-related respiratory depression and, less commonly, bradycardia are possible side-effects, potentially more likely in older women (particularly over 70 years).

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Local; Anesthetics, Intravenous; Cohort Studies; Female; Humans; Middle Aged; Piperidines; Remifentanil; Retrospective Studies; Suburethral Slings; Treatment Outcome; Urinary Incontinence

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Female; Humans; Indans; Male; Middle Aged; Phenylcarbamates; Piperidines; Rivastigmine; Urinary Incontinence

Clinicians often encounter patients with dementia and urge incontinence who might benefit from both an anticholinergic medication and a cholinesterase inhibitor. At first glance, this combination would seem to violate basic principles of geriatric pharmacology, as the drugs appear to be working at cross-purposes and anticholinergic medications are notorious for worsening cognitive function in susceptible patients. A case is presented and discussed in which this combination was clinically effective and pharmacologically sound.

Topics: Aged; Benzhydryl Compounds; Cholinesterase Inhibitors; Cresols; Dementia; Donepezil; Drug Interactions; Drug Therapy, Combination; Female; Humans; Indans; Muscarinic Antagonists; Phenylpropanolamine; Piperidines; Tolterodine Tartrate; Urinary Incontinence

To evaluate the effect of St. John's wort (SJW), an effective and safe herbal antidepressant, on rat bladder contractility. Recent data have suggested a strong association between depression and urinary incontinence.. Strips were cut from the bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation (EFS) and, in some experiments, by exogenous alpha,beta (alpha,beta)-methylene adenosine triphosphate.. St. John's wort was significantly more active in inhibiting the EFS-induced contractions than the alpha,beta-methylene adenosine triphosphate-induced contractions, suggesting both a presynaptic site of action and a direct inhibition of bladder smooth muscle. The inhibitory effect of SJW on EFS-induced contractions was unaffected by methysergide, haloperidol, phentolamine plus propranolol (antagonists that block the action of the neurotransmitters 5-hydroxytriptamine, dopamine, and noradrenaline on their own receptors), the L-type calcium channel antagonist verapamil, capsazepine (which blocks the vanilloid receptor), or cannabinoid CB1 receptor antagonist SR141716A. However, the opioid receptor antagonist naloxone significantly reduced the inhibitory effect of SJW on EFS-induced contractions. Among the chemical constituents of SJW tested, hyperforin and, to a lesser extent, the flavonoid kaempferol showed inhibitory effects.. The results of our study demonstrated that SJW inhibits excitatory transmission of the rat urinary bladder and also directly inhibits smooth muscle contractility. The inhibitory effect on excitatory transmission could involve, at least in part, opioid receptors. SJW may be evaluated for its possible use in treating urinary incontinence in depressed patients.

Topics: Acetylcholine; Adenosine Triphosphate; Animals; Anthracenes; Antidepressive Agents; Atropine; Bridged Bicyclo Compounds; Capsaicin; Depression; Electric Stimulation; Female; Haloperidol; Hypericum; Kaempferols; Male; Methysergide; Muscle Contraction; Muscle, Smooth; Naloxone; Perylene; Phentolamine; Phloroglucinol; Piperidines; Plant Extracts; Propranolol; Pyrazoles; Quercetin; Rats; Rats, Wistar; Rimonabant; Rutin; Terpenes; Tetrodotoxin; Urinary Bladder; Urinary Incontinence; Verapamil

Topics: Conscious Sedation; Female; Humans; Hypnotics and Sedatives; Piperidines; Remifentanil; Urinary Incontinence

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Cholinesterase Inhibitors; Donepezil; Humans; Indans; Inpatients; Male; Piperidines; Urinary Incontinence

Concentration-response curves to acetylcholine, and responses to electrical field stimulation (EFS) were compared in detrusor muscle strips, from control patients and those with idiopathic detrusor instability (IDI). Responses were similar in both groups. However, atropine abolished responses to EFS in 80% of control but only 33% of IDI patients (P>0.05), with the residual atropine-resistant response in most IDI patients abolished by tetrodotoxin. The post-atropine residual response was unaffected by the tachykinin NK-2 receptor antagonist SR48968. Despite the known existence of NK-2 receptors in the human detrusor, there was no evidence for tachykinin contribution to EFS-induced contractions.

Topics: Acetylcholine; Aged; Benzamides; Case-Control Studies; Dose-Response Relationship, Drug; Electric Stimulation; Female; Humans; Middle Aged; Muscle Contraction; Piperidines; Receptors, Cholinergic; Receptors, Neurokinin-2; Tachykinins; Urinary Bladder; Urinary Incontinence

M(3) muscarinic receptors mediate cholinergic-induced contraction in most smooth muscles. However, in the denervated rat bladder, M(2) receptors participate in contraction because M(3)-selective antagonists [para-fluoro-hexahydro-sila-diphenidol (p-F-HHSiD) and 4-DAMP] have low affinities. However, the affinity of the M(2)-selective antagonist methoctramine in the denervated bladder is consistent with M(3) receptor mediating contraction. It is possible that two pathways interact to mediate contraction: one mediated by the M(2) receptor and one by the M(3) receptor. To determine whether an interaction exists, the inhibitory potencies of combinations of methoctramine and p-F-HHSiD for reversing cholinergic contractions were measured. In normal bladders, all combinations gave additive effects. In denervated bladders, synergistic effects were seen with the 10:1 and 1:1 (methoctramine:p-F-HHSiD wt/wt) combinations. After application of the sarcoplasmic reticulum ATPase inhibitor thapsigargin to normal tissue, the 10:1 and 1:1 ratios became synergistic, mimicking denervated tissue. Thus in normal bladders both M(2) and M(3) receptors can induce contraction. In the denervated bladder, the M(2) and the M(3) receptors interact in a facilitatory manner to mediate contraction.

Topics: Animals; Carbachol; Cholinergic Agents; Denervation; Female; In Vitro Techniques; Muscarinic Antagonists; Muscle Contraction; Muscle, Smooth; Piperidines; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptors, Muscarinic; Second Messenger Systems; Signal Transduction; Urinary Bladder; Urinary Incontinence

In order to clarify the role of supraspinal tachykinins in volume-induced micturition and in bladder hyperactivity secondary to bladder outlet obstruction, conscious, normal, female Sprague-Dawley rats were investigated cystometrically before and after intracerebroventricular administration of RP 67,580, a selective antagonist of neurokinin (NK)-1 receptors and/or SR 48,968, a selective antagonist of NK-2 receptors. In normal rats, RP 67,580 or SR 48,968, at a dose of 2 nmol, caused no marked changes in cystometric parameters. Higher doses (up to 20 nmol) caused dose-dependent decreases in micturition pressure and increased bladder capacity, micturition volume and residual urine. A combination of the two drugs, each at a dose of 2 nmol, significantly decreased micturition pressure and increased bladder capacity. In rats with bladder outlet obstruction, the antagonists suppressed micturition dose-dependently, producing urinary retention in two out of eight rats already at a dose of 2 nmol. At a dose of 20 nmol, dribbling incontinence, due to urinary retention, was seen in five out of ten rats. A combination of the two drugs (2 nmol of each drug) caused urinary retention in three out of nine animals and significantly increased bladder capacity, micturition volume and residual volume. The results suggest that outflow obstruction in rats increases the effects of tachykinins in supraspinal structures involved in micturition, and that antagonism of supraspinal NK-receptors may depress the micturition reflex. Whether or not this implies that supraspinal NK-receptors can be targets for drugs aimed for inhibiting bladder hyperactivity in humans should be explored.

Topics: Analgesics; Animals; Benzamides; Catheterization; Female; Indoles; Isoindoles; Methylene Blue; Neurokinin-1 Receptor Antagonists; Piperidines; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-2; Tachykinins; Tissue Distribution; Urinary Bladder; Urinary Bladder Neck Obstruction; Urinary Incontinence; Urination

Donepezil has been licensed for use in Japan to improve cognitive function since 1999. Among 94 patients with probable Alzheimer's disease who we treated with donepezil, seven patients developed urinary incontinence, although this event was transient in most patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Donepezil; Female; Humans; Indans; Male; Nootropic Agents; Piperidines; Urinary Incontinence

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Comorbidity; Donepezil; Down Syndrome; Female; Humans; Indans; Male; Middle Aged; Piperidines; Urinary Incontinence

The intraperitoneal administration of cyclophosphamide (150 mg/kg, 48 h before cystometry) induced detrusor hyperreflexia in urethane-anaesthetized rats. Intrathecal administration of the selective tachykinin NK1 receptor antagonist, GR 82,334 ([D-Pro9(spiro-gamma-lactam)Leu10,Trp11]physalaemin-(1-11)) (1 nmol/rat i.t.) had no significant effect on micturition in normal rats but increased the volume threshold In cyclophosphamide-treated rats. Another tachykinin NK1 receptor antagonist, RP 67,580 ((3aR,7aR)-7,7-diphenyl-2-[1-imino-2(2-methoxyphenyl)ethyl]+ ++perhydroisoindol -4-one) (10 nmol/rat i.t.) increased the volume threshold to a similar extent in both vehicle- and cyclophosphamide-treated animals. The tachykinin NK2 receptor antagonist, SR 48,968 (S7-N-methyl-N[4-(acetylamino-4-phenylpiperidino)-2-(3,4- dichlorophenyl)butyl]benzamide hydrochloride (10 nmol/rat i.t.) did not modify micturition parameters in normal rats but antagonized bladder hyperreflexia in cyclophosphamide-treated animals; SR 48,968 restored the volume threshold for the micturition reflex to values close to control values. SR 48,965 (R7-N-methyl-N[4-(acetylamino-4-phenylpiperidino)-2-(3,4- dichlorophenyl)butyl]benzamide hydrochloride) (10 nmol/rat i.t.), the enantiomer of SR 48,968 devoid of affinity for tachykinin NK2 receptors, was inactive. 2-Amino-5-phosphonovaleric acid (25 and 250 nmol/rat i.t.), a selective antagonist of NMDA receptors, augmented the volume threshold both in controls and in rats with detrusor hyperreflexia; after administration of this antagonist, however, the volume threshold in cyclophosphamide-treated animals was still lower than in controls. Intravenous administration of SR 48,968, RP 67,580, or the combined administration of SR 48,968 and RP 67,580 had no effect on cystometry variables either in rats with detrusor hyperreflexia or in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Amino-5-phosphonovalerate; Animals; Benzamides; Cyclophosphamide; Cystitis; Indoles; Injections, Intravenous; Injections, Spinal; Isoindoles; Male; Neurokinin-1 Receptor Antagonists; Physalaemin; Piperidines; Rats; Rats, Wistar; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Spinal Cord; Urinary Incontinence; Urination

The author used Imodium in a clinical trial for the treatment of urinary incontinence following radical prostatectomies, urinary and faecal incontinence due to carcinoma or cerebral accident in history. The drug significantly improved incontinence and did not cause adverse effects. On the basis of the similarity of innervation the author opines that loperamide also influences the function of detrusor and/or bladder orifice besides exerting an antiperistaltic and anal sphincter influencing action.

Topics: Aged; Fecal Incontinence; Female; Humans; Hungary; Loperamide; Male; Middle Aged; Piperidines; Urinary Incontinence

This study examined 75 children with daytime wetting and particularly those with some form of bladder neck incompetence. There was a good response in 75% of cases to Eskornade (containing phenylpropanolamine, an alpha adrenergic agonist), but a lesser response in children with bladder instability. Large doses of this preparation have sometimes been necessary to produce urinary continence and side effects, although common, were usually minor and transient.

Topics: Adolescent; Adult; Child; Child, Preschool; Delayed-Action Preparations; Drug Combinations; Female; Humans; Male; Phenylpropanolamine; Piperidines; Quaternary Ammonium Compounds; Retrospective Studies; Urinary Incontinence

Topics: Antipsychotic Agents; Fecal Incontinence; Humans; Intellectual Disability; Middle Aged; Phenothiazines; Piperidines; Schizophrenia; Urinary Incontinence

Topics: Adult; Benzene Derivatives; Carboxylic Acids; Cystoscopy; Female; Flavonoids; Humans; Male; Middle Aged; Piperidines; Quaternary Ammonium Compounds; Transducers; Urethra; Urinary Bladder; Urinary Incontinence; Urinary Incontinence, Stress; Urography