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Clinical Interventions in Aging 2011Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for... (Review)
Review
Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the α(1)-adrenergic receptor antagonists. Silodosin is a new α(1)-adrenergic receptor antagonist that is selective for the α(1A)-adrenergic receptor. By antagonizing α(1A)-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the α(1A)-adrenergic receptor than for the α(1B)-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by α(1B)-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective α(1A)-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH.
Topics: Adrenergic Antagonists; Aged; Drug-Related Side Effects and Adverse Reactions; Humans; Indoles; Male; Middle Aged; Outcome Assessment, Health Care; Prostatic Hyperplasia; Randomized Controlled Trials as Topic
PubMed: 21753871
DOI: 10.2147/CIA.S13803 -
The Canadian Journal of Urology Oct 2010
Topics: Adrenergic alpha-1 Receptor Antagonists; Drug Discovery; History, 20th Century; History, 21st Century; Humans; Japan; Sulfonamides; Tamsulosin; Urology
PubMed: 20974024
DOI: No ID Found -
British Journal of Clinical Pharmacology 1979The clinical pharmacology of labetalol has been evaluated using pharmacological and physiological test methods. Labetalol displaces the log dose-response curves to the... (Review)
Review
The clinical pharmacology of labetalol has been evaluated using pharmacological and physiological test methods. Labetalol displaces the log dose-response curves to the right of isoprenaline-induced increases in heart rate, cardiac output and decreases in diastolic BP. The similarity in the displacements of these curves suggests labetalol has non-selective β-adrenoceptor-blocking properties. Labetalol inhibits exercise-induced increases in heart rate and systolic BP, inhibits tilt tachycardia and that associated with Valsalva's manoeuvre. Direct comparison with propranolol using the methods above have shown that the β-adrenoceptor-blocking effect of labetalol is qualitatively similar to that of propranolol but that propranolol is more potent weight for weight to the order of 4 to 6:1 propranolol:labetalol. In respect of their effects on respiratory function, labetalol and propranolol are qualitatively different; whereas propranolol increases airways resistance in equipotent β-adrenoceptor-blocking doses, labetalol does not. Labetalol displaces the log dose-response curves of phenylephrine and noradrenaline-induced increases in systolic and diastolic BPs to the right consistent with an α-adrenoceptor-blocking action. Labetalol inhibits increases in BP due to a cold stimulus, whereas propranolol does not. The combined α- and β-adrenoceptor-blocking effect of labetalol after acute and chronic administration leads to reductions in BP and peripheral resistance but little change in heart rate or cardiac output at rest. During exercise, increases in BP and heart rate are attenuated but cardiac output increases are only significantly diminished at high levels of exercise. Labetalol is less lipophylic than propranolol, with a partition coefficient of 1.2. It is almost completely metabolized being extensively conjugated.
Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Ethanolamines; Hemodynamics; Humans; Kinetics; Labetalol; Sympathetic Nervous System
PubMed: 43165
DOI: No ID Found -
Current Medicinal Chemistry 2011The purine ribonucleoside adenosine (Ado) has been recognized for its regulatory functions in situations of cellular stress like ischemia, hypoxia and inflammation. The... (Review)
Review
The purine ribonucleoside adenosine (Ado) has been recognized for its regulatory functions in situations of cellular stress like ischemia, hypoxia and inflammation. The importance of extracellular Ado as a modulator in the immune system is a theme of great appreciation and the focus of recent increasing interest in the field of gastrointestinal inflammation. In this review, the different aspects of Ado signaling during inflammatory responses in the gut are discussed, considering the contribution of the four known Ado receptors (ARs; A(1), A(2A), A(2B), and A(3)), their mechanisms and expression patterns. Activation of these receptors in epithelial cells as well as in immune cells recruited to the inflamed intestinal mucosa determines the overall effect, ranging from a protective, anti-inflammatory modulation to a strong pro-inflammatory induction. Here we present the current advances in agonists and antagonists development and their potential therapeutic application studied in animal models of intestinal inflammation. In addition, alternative complementary approaches to manipulate such a complex signaling system are discussed, for example, the use of AR allosteric modulators or interference with Ado metabolism. Special features of the gut environment are taken into account: the contribution of diet components; the involvement of Ado in intestinal infections; the interactions with the gut microbiome, particularly, the recent exciting finding that an intestinal bacterium can directly produce extracellular Ado in response to host defense mechanisms in an inflammation scenario. Understanding each component of this dynamic system will broaden the possibilities for applying Ado signaling as a therapeutic target in gut inflammation.
Topics: Adenosine; Adrenergic Agonists; Adrenergic Antagonists; Animals; Humans; Inflammatory Bowel Diseases; Receptors, Purinergic P1; Structure-Activity Relationship
PubMed: 21649583
DOI: 10.2174/092986711796011274 -
CA: a Cancer Journal For Clinicians May 2013Hot flashes are prevalent and severe symptoms that can interfere with mood, sleep, and quality of life for women and men with cancer. The purpose of this article is to... (Review)
Review
Hot flashes are prevalent and severe symptoms that can interfere with mood, sleep, and quality of life for women and men with cancer. The purpose of this article is to review existing literature on the risk factors, pathophysiology, and treatment of hot flashes in individuals with cancer. Electronic searches were conducted to identify relevant English-language literature published through June 15, 2012. Results indicated that risk factors for hot flashes in cancer include patient-related factors (eg, age, race/ethnicity, educational level, smoking history, cardiovascular risk including body mass index, and genetics) and disease-related factors (eg, cancer diagnosis and dose/type of treatment). In addition, although the pathophysiology of hot flashes has remained elusive, these symptoms are likely attributable to disruptions in thermoregulation and neurochemicals. Therapies that have been offered or tested fall into 4 broad categories: pharmacological, nutraceutical, surgical, and complementary/behavioral strategies. The evidence base for this broad range of therapies varies, with some treatments not yet having been fully tested or showing equivocal results. The evidence base surrounding all therapies is evaluated to enhance hot flash treatment decision-making by clinicians and patients.
Topics: Adrenergic Antagonists; Anticonvulsants; Antidepressive Agents; Autonomic Nerve Block; Body Temperature Regulation; Cholinergic Antagonists; Cognitive Behavioral Therapy; Complementary Therapies; Hot Flashes; Humans; Neoplasms; Phytotherapy; Risk Factors; Stellate Ganglion; Vitamins
PubMed: 23355109
DOI: 10.3322/caac.21171 -
Naunyn-Schmiedeberg's Archives of... Dec 2009Doxazosin and related, quinazoline-based alpha(1)-adrenoceptor antagonists can induce apoptosis in prostate and various other normal, benign, smooth muscle, endothelial...
Doxazosin and related, quinazoline-based alpha(1)-adrenoceptor antagonists can induce apoptosis in prostate and various other normal, benign, smooth muscle, endothelial and malignant cells. Such apoptosis-inducing effects occur independently of alpha(1)-adrenoceptor antagonism and typically require much high concentrations than those required for receptor occupancy. Several studies have invested efforts towards the elucidation of the molecular mechanisms underlying doxazosin-induced apoptosis. These include various tumor cells, cardiomyocytes, endothelial cells and bladder smooth muscle cells. While the high concentrations of doxazosin required to induce apoptosis challenge the use of this and related drugs for clinical optimization of apoptosis induction, such quinazoline structure may represent chemical starting points to develop more potent apoptosis-inducing agents free of alpha(1)-adrenoceptor antagonistic action and suitable for cancer treatment with minimal and well-tolerated side effects.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Antineoplastic Agents; Apoptosis; Doxazosin; Humans; Neoplasms; Quinazolines
PubMed: 19904527
DOI: 10.1007/s00210-009-0462-4 -
British Journal of Pharmacology Jun 2012Antibodies against cholinergic and adrenergic receptors (adrenoceptors) are frequent in serum of patients with chronic heart failure. Their prevalence is associated with... (Review)
Review
Antibodies against cholinergic and adrenergic receptors (adrenoceptors) are frequent in serum of patients with chronic heart failure. Their prevalence is associated with Chagas' disease, idiopathic dilated cardiomyopathy (DCM), and ischaemic heart disease. Among the epitopes targeted are first and second extracellular loops of the β-adrenergic (β-adrenoceptor) and M2 muscarinic receptor. β(1)-adrenoceptor autoantibodies affect radioligand binding and cardiomyocyte function similar to agonists. Corresponding rodent immunizations induce symptoms compatible with chronic heart failure that are reversible upon removal of the antibodies, transferable via the serum and abrogated by adrenergic antagonists. In DCM patients, prevalence and stimulatory efficacy of β(1)-adrenoceptor autoantibodies are correlated to the decline in cardiac function, ventricular arrhythmia and higher incidence of cardiac death. In conclusion, such autoantibodies seem to cause or promote chronic human left ventricular dysfunction by acting on their receptor targets in a drug-like fashion. However, the pharmacology of this interaction is poorly understood. It is unclear how the autoantibodies trigger changes in receptor activity and second messenger coupling and how that is related to the pathogenesis and severity of the associated diseases. Here, we summarize the available evidence regarding these issues and discuss these findings in the light of recent knowledge about the conformational activation of the human β(2)-adrenoceptor and the properties of bona fide cardiopathogenic autoantibodies derived from immune-adsorption therapy of DCM patients. These considerations might contribute to the conception of therapy regimen aimed at counteracting or neutralizing cardiopathogenic receptor autoantibodies.
Topics: Adrenergic Antagonists; Allosteric Regulation; Animals; Autoantibodies; Autonomic Nervous System; Heart Diseases; Humans; Myocardial Contraction; Receptors, Adrenergic; Receptors, Cholinergic
PubMed: 22220626
DOI: 10.1111/j.1476-5381.2012.01828.x -
Yakugaku Zasshi : Journal of the... Mar 2006Alpha(1)-adrenoceptors are widely distributed in the human body and play important physiologic roles. Three alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and... (Review)
Review
Alpha(1)-adrenoceptors are widely distributed in the human body and play important physiologic roles. Three alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) have been cloned and show different pharmacologic profiles. In addition, a putative alpha(1)-adrenoceptor (alpha(1L) subtype) has also been proposed. Recently, three drugs (tamsulosin, naftopidil, and silodosin) have been developed in Japan for the treatment of urinary obstruction in patients with benign prostatic hyperplasia. In this review, we describe recent alpha(1)-adrenoceptor subclassifications and the pharmacologic characteristics (subtype selectivity and clinical relevance) of alpha(1)-adrenoceptor antagonists.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Amino Acid Sequence; Animals; Cloning, Molecular; Drug Design; Drug Tolerance; Humans; Male; Molecular Sequence Data; Naphthalenes; Piperazines; Prostatic Hyperplasia; Receptors, Adrenergic, alpha-1; Sulfonamides; Tamsulosin; Urethral Obstruction
PubMed: 16518082
DOI: 10.1248/yakushi.126.187 -
British Journal of Pharmacology Mar 2012α(1)-Adrenoceptors are involved in numerous physiological functions, including micturition. However, the pharmacological profile of the α(1)-adrenoceptor subtypes... (Review)
Review
α(1)-Adrenoceptors are involved in numerous physiological functions, including micturition. However, the pharmacological profile of the α(1)-adrenoceptor subtypes remains controversial. Here, we review the literature regarding α(1)-adrenoceptors in the lower urinary tract from the standpoint of α(1L) phenotype pharmacology. Among three α(1)-adrenoceptor subtypes (α(1A), α(1B) and α(1D)), α(1a)-adrenoceptor mRNA is the most abundantly transcribed in the prostate, urethra and bladder neck of many species, including humans. In prostate homogenates or membrane preparations, α(1A)-adrenoceptors with high affinity for prazosin have been detected as radioligand binding sites. Functional α(1)-adrenoceptors in the prostate, urethra and bladder neck have low affinity for prazosin, suggesting the presence of an atypical α(1)-adrenoceptor phenotype (designated as α(1L)). The α(1L)-adrenoceptor occurs as a distinct binding entity from the α(1A)-adrenoceptor in intact segments of variety of tissues including prostate. Both the α(1L)- and α(1A)-adrenoceptors are specifically absent from Adra1A (α(1a)) gene-knockout mice. Transfection of α(1a)-adrenoceptor cDNA predominantly expresses α(1A)-phenotype in several cultured cell lines. However, in CHO cells, such transfection expresses α(1L)- and α(1A)-phenotypes. Under intact cell conditions, the α(1L)-phenotype is predominant when co-expressed with the receptor interacting protein, CRELD1α. In summary, recent pharmacological studies reveal that two distinct α(1)-adrenoceptor phenotypes (α(1A) and α(1L)) originate from a single Adra1A (α(1a)-adrenoceptor) gene, but adrenergic contractions in the lower urinary tract are predominantly mediated via the α(1L)-adrenoceptor. From the standpoint of phenotype pharmacology, it is likely that phenotype-based subtypes such as the α(1L)-adrenoceptor will become new targets for drug development and pharmacotherapy.
Topics: Adrenergic alpha-1 Receptor Antagonists; Animals; Humans; Phenotype; Prazosin; Receptors, Adrenergic, alpha-1; Urinary Tract
PubMed: 21745191
DOI: 10.1111/j.1476-5381.2011.01591.x -
Brain Research Oct 2009Post-traumatic stress disorder (PTSD) is a prevalent anxiety disorder that results in multiple disabling symptoms. Research into the underlying neurobiology has... (Review)
Review
Post-traumatic stress disorder (PTSD) is a prevalent anxiety disorder that results in multiple disabling symptoms. Research into the underlying neurobiology has implicated dysregulation in multiple neurotransmitter systems including norepinephrine, serotonin, and glutamate as well as the hypothalamic-pituitary axis. Understanding how these biological systems interact with each other and how they may affect key neural structures, such as the amygdala, hippocampus, and prefrontal cortex, to produce post-traumatic symptoms is critical for the development of effective pharmacological treatments. We briefly discuss the proposed biological dysfunctions underlying PTSD and how agents that target these dysfunctions may be utilized in PTSD. We then provide a review of the different pharmacological agents that have been investigated in PTSD. These drugs include: antidepressants, anti-adrenergic agents, anticonvulsants, benzodiazepines, atypical antipsychotics, and novel agents.
Topics: Adrenergic Antagonists; Anticonvulsants; Antidepressive Agents; Glutamic Acid; Humans; Hypothalamo-Hypophyseal System; Norepinephrine; Pituitary-Adrenal System; Serotonin; Stress Disorders, Post-Traumatic
PubMed: 19332035
DOI: 10.1016/j.brainres.2009.03.037