Urethral function and histopathology in aged female rats as a stress urinary incontinence model.

Objective: Stress urinary incontinence (SUI) is a common disease condition in elderly women, suggesting that its etiology may be linked to aging. To investigate the hypothesis that urethral dysfunction and histopathological changes are possible contributors to SUI in elderly women, several parameters of urethral function, as well as histological parameters, were compared between young and aged rats.

Methods: Virgin female rats were examined at 3 different ages, namely 3, 12, and 24 months, corresponding to young, middle-aged, and aged rats, respectively.

Effects of α1-adrenoceptor antagonists on phenylephrine-induced salivary secretion and intraurethral pressure elevation in anesthetized rats.

α(1)-Adrenoceptor antagonists are widely used for the treatment of voiding dysfunction associated with benign prostatic hyperplasia. Activation of α(1)-adrenoceptors is reported to induce salivary secretion in rats and humans. However, the effects of α(1)-adrenoceptor antagonists on salivary secretion remain unknown.

Optimization of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin V2 receptor agonists and discussion of their binding modes.

A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives were optimized to achieve potent agonistic activity, both in vitro and in vivo, for the arginine vasopressin V(2) receptor, resulting in the eventual discovery of compound 1g. Molecular modeling of compound 1g with V(2) receptor was also examined to evaluate the binding mode of this series of compounds.

Zolpidem increases bladder capacity and decreases urine excretion in rats.

Aims: To clarify the effects of zolpidem, a gamma-aminobutyric acid (GABA)(A) receptor agonist, on bladder function, and urine production, we investigated the effects of zolpidem administration on bladder overactivity induced by cerebral infarction (CI) and on urine excretion increased by water overloading in Wistar rats.

Methods: CI was induced by left middle cerebral artery occlusion. The effects on bladder function of zolpidem alone or in combination with the GABA(A) receptor antagonist bicuculline, were then examined in the CI rats using cystometry.

Synthesis and structure-activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetic acid as selective arginine vasopressin V2 receptor agonists.

A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives was synthesized, and their structure-activity relationships were examined in order to identify potent and selective arginine vasopressin V(2) receptor agonists. Attempts to substitute other chemical groups in place of the 2-pyridilmethyl moiety of 1a led to the discovery that potent V(2) binding affinity could be obtained with a wide range of functional groups. This structural tolerance allowed for the manipulation of other attributes, such as selectivity against V(1a) receptor affinity or avoidance of the undesirable inhibition of cytochrome P450 (CYP), without losing potent affinity for the V(2) receptor.

Preparation of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives as novel arginine vasopressin V(2) receptor agonists.

The present work describes the discovery of novel series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin (AVP) V(2) receptor agonists. By replacing the amide juncture in YM-35278 with a direct ring connection gave compound 10a, which acts as a V(2) receptor agonist. These studies provided the potent, orally active non-peptidic V(2) receptor agonists 10a and 10j.

In vivo studies on the effects of alpha1-adrenoceptor antagonists on pupil diameter and urethral tone in rabbits.

Alpha1-adrenoceptors mediate contraction of iris dilator smooth muscle and hence pupil dilatation. We compared the ability of i.v.

Characterization of the pharmacology of YM-198313 on volume-regulated anion channels.

Activation of the volume-regulated anion channels (VRAC) is considered to be involved in arrhythmia, but it has not yet been fully elucidated because of the lack of its high affinitive and selective compounds. A newly synthesized compound, YM-198313 (sodium 4-({[2-(methylthio)benzyl]amino}-5-[(1-phenylethyl)thio]isothiazol-3-olate), strongly inhibited VRAC in HeLa cells with an IC50 of 3.03+/-0.