Comparison of ??1-Adrenoceptor Agonists in Canine Urethral Pressure Profilometry and Abdominal Leak Point Pressure Models

Brune, Michael E.; O’Neill, Alyssa B.; Gauvin, Donna M.; Katwala, Sweta P.; Altenbach, Robert J.; Brioni, Jorge D.; Hancock, Arthur A.; Sullivan, James P.

doi:10.1097/00005392-200110000-00090

Cited by 10 publications

(16 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Leak point pressure again has been utilised both clinically (Khullar & Cardozo, 1998) and preclinically in a number of species (Brune et al ., 2001; Buckner et al ., 2002; Damaser et al ., 2003). The methods utilised to induce leak in animal models can vary however, ranging from simply applying pressure to the abdomen with the palm of the hand in dogs (Brune et al ., 2001) to placing rats on a tilt table with a pressure clamp (Chermansky et al ., 2004) or utilising a blood pressure (BP) cuff (Rawlings et al ., 2001). In all cases however, leak point pressure measurements are taken as the peak bladder pressure prior to leak, measured using a bladder cannula, which can also be used to fill the bladder prior to leak point measurement.…”

Section: Animal Models Of Lower Urinary Tract Function and Dysfunctionmentioning

confidence: 99%

Animal models in urological disease and sexual dysfunction

McMurray¹,

Casey²,

Naylor³

2006

British J Pharmacology

View full text Add to dashboard Cite

There are several conditions associated with dysfunction of the lower urinary tract or which result in a reduction in the ability to engage in satisfactory sexual function and result in significant bother to sufferers, partners and/or carers. This review describes some of the animal models that may be used to discover safe and effective medicines with which to treat them. While alpha adrenoceptor antagonists and 5-alpha-reductase inhibitors deliver improvement in symptom relief in benign prostatic hyperplasia sufferers, the availability of efficacious and well-tolerated medicines to treat incontinence is less well served. Stress urinary incontinence (SUI) has no approved medical therapy in the United States and overactive bladder (OAB) therapy is limited to treatment with muscarinic antagonists (anti-muscarinics). SUI and OAB are characterised by high prevalence, a growing ageing population and a strong desire from sufferers and physicians for more effective treatment options. High patient numbers with low presentation rates characterizes sexual dysfunction in men and women. The introduction of Viagrat in 1998 for treating male erectile dysfunction and the success of the phosphodiesterase type 5 inhibitor class (PDE5 inhibitor) have indicated the willingness of sufferers to seek treatment when an effective alternative to injections and devices is available. The main value of preclinical models in discovering new medicines is to predict clinical outcomes. This translation can be established relatively easily in areas of medicine where there are a large number of drugs with different underlying pharmacological mechanisms in clinical usage. However, apart from, for example, the use of PDE5 inhibitors to treat male erectile dysfunction and the use of antimuscarinics to treat OAB, this clinical information is limited. Therefore, current confidence in existing preclinical models is based on our understanding of the biochemical, physiological, pathophysiological and psychological mechanisms underlying the conditions in humans and how they are reflected in preclinical models. Confidence in both the models used and the pharmacological data generated is reinforced if different models of related aspects of the same disorder generate confirmatory data. However, these models will only be fully validated in retrospect once the pharmacological agents they have helped identify are tested in humans. Animal models of lower urinary tract function and dysfunctionThe two major functions of the lower urinary tract (LUT) are to store urine and, periodically and at an opportune moment, to empty or expel the stored urine. This involves a complex pattern of efferent (motor) and afferent (sensory) signalling in both the autonomic and somatic nervous systems. The nerves involved form part of a reflex pathway, with an incorporated conscious control component, which can either maintain the bladder in an accommodating state, enabling urine storage at low intravesical pressure, or which can initiate micturition by relaxing the outflow region (...

show abstract

Section: Animal Models Of Lower Urinary Tract Function and Dysfunctionmentioning

confidence: 99%

Animal models in urological disease and sexual dysfunction

McMurray¹,

Casey²,

Naylor³

2006

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…1 Therapy for urinary incontinence in female dogs has centered on the use of estrogens and a-agonist drugs to increase the tone of urethral smooth muscle. [4][5][6] PPA has been used to treat women and dogs with urethral sphincter mechanism incompetence for the last 30 years. 2,3 In the last 10 years, estrogen usage has decreased and phenylpropanolamine (PPA), a nonselective a-agonist that has been shown to increase urethral closure pressure in incontinent dogs has been used more commonly.…”

mentioning

confidence: 99%

“…[4][5][6][17][18][19][20] It has been used to evaluate the effectiveness of various drugs for treatment of incontinence and to grade severity of disease. [4][5][6][17][18][19][20] It has been used to evaluate the effectiveness of various drugs for treatment of incontinence and to grade severity of disease.…”

mentioning

confidence: 99%

Effect of Phenylpropanolamine and Pseudoephedrine on the Urethral Pressure Profile and Continence Scores of Incontinent Female Dogs

Byron

March

Chew

et al. 2007

Veterinary Internal Medicne

View full text Add to dashboard Cite

Background: Traditionally, treatment of urinary incontinence in spayed female dogs has been to increase urethral sphincter tone with estrogen compounds or a-agonists. Phenylpropanolamine (PPA) is the most frequently used a-agonist for this condition, but increased cost and decreased availability of PPA as an over-the-counter medication have prompted interest in alternative therapies that may provide the same degree of efficacy. Pseudoephedrine (PD), an a-agonist and stereoisomer of ephedrine, is more cost-effective and available without a prescription. Hypothesis: PD will not differ from PPA in its effects on urodynamic variables and owner-reported continence scores or in observed adverse effects. Animals: Nine spayed female dogs with a history of urinary incontinence drawn from the clinical patient population at the Veterinary Teaching Hospital at The Ohio State University. Methods: A randomized, double-blind crossover study evaluating changes in urodynamic variables, owner-reported continence score, and adverse effects in dogs treated with 1.5 mg/kg PO q8h PPA or PD. Results: Changes in maximum urethral closure pressure and functional area after PPA therapy were significantly higher than after PD therapy. There was no change in the functional profile length after either treatment. There was a significant increase in the continence score after PPA therapy, but not after PD therapy. More adverse effects were observed in dogs treated with PD than with PPA. Conclusions and Clinical Importance: Although some dogs clinically improved, lack of statistically significant changes in urodynamic variables and owner perception of continence as well as the increased incidence of adverse effects make PD a less satisfactory alternative to PPA for the treatment of urinary incontinence in female dogs.

show abstract

“…The α 1A , α 1B , and α 1D receptors are all acting mainly on smooth muscle cells leading to vasoconstriction, bronchospasms, and decreased motility in the GI tract. Subtype α 1A receptor selective agonists have been shown to be efficacious in in vivo models of stress urinary incontinence (SUI) . However, full α 1A receptor agonists possess a slender therapeutic index over α 1A ‐induced cardiovascular effects.…”

Section: Miscellaneous Targetsmentioning

confidence: 99%

Indanes—Properties, Preparation, and Presence in Ligands for G Protein Coupled Receptors

Vilums

Heuberger

Heitman

et al. 2015

Medicinal Research Reviews

View full text Add to dashboard Cite

The indane (2,3-dihydro-1H-indene) ring system is an attractive scaffold for biologically active compounds due to the combination of aromatic and aliphatic properties fused together in one rigid system. This bicyclic structure provides a wide range of possibilities to incorporate specific substituents in different directionalities, thus being an attractive scaffold for medicinal chemists. Notably, many indane-based compounds are being used in the clinic to treat various diseases, such as indinavir, an HIV-1 protease inhibitor; indantadol, a potent Monoamine Oxidase (MAO)-inhibitor; the amine uptake inhibitor indatraline; and the ultra-long-acting β-adrenoceptor agonist indacaterol. Given the diversity of targets these drugs act on, one could argue that the indane ring system is a privileged substructure. In the present review, the synthetic and medicinal chemistry of the indane ring system is described. In more detail, it contains a comprehensive overview of compounds bearing the indane substructure with G protein coupled receptor (GPCR) activity, with particular emphasis on their structure-activity relationships (SAR).

show abstract

Comparison of ??1-Adrenoceptor Agonists in Canine Urethral Pressure Profilometry and Abdominal Leak Point Pressure Models

Cited by 10 publications

References 20 publications

Animal models in urological disease and sexual dysfunction

Animal models in urological disease and sexual dysfunction

Effect of Phenylpropanolamine and Pseudoephedrine on the Urethral Pressure Profile and Continence Scores of Incontinent Female Dogs

Indanes—Properties, Preparation, and Presence in Ligands for G Protein Coupled Receptors

Contact Info

Product

Resources

About