Biomaterial Database

Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. 2004

Claus G Roehrborn, and Debra A Schwinn

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9110, USA. claus.reohrborn@utsouthwestern.edu

OBJECTIVE We provide a comprehensive overview of the role of alpha1-adrenergic receptors (alpha1ARs) as critical mediators of lower urinary tract symptoms (LUTS) and pathophysiology in benign prostatic hyperplasia (BPH), and we review the pharmacological antagonists of alpha1ARs. METHODS A review was performed of pertinent studies in the literature relating to the pathophysiology of LUTS and BPH, focusing on the role of alpha1ARs, and of clinical trial and practice data evaluating the different agents that inhibit these receptors. RESULTS Further characterization of the alpha1AR gene family indicates that 3 receptor subtypes exist in humans. Their different distribution between urinary tract and cardiovascular tissues has provided a strategy for the development of improved therapeutic agents. Since excessive activity of the alpha1aAR and alpha1dAR subtypes appears to be a common feature in symptomatic BPH and alpha1aARs are enriched in prostatic tissue, drugs that demonstrate high alpha1aAR selectivity have attracted attention. Tamsulosin, which has high affinity for alpha1aAR and alpha1dAR subtypes but not for alpha1bAR, shows efficacy similar to the nonsubtype selective agents terazosin and doxazosin. It is associated with fewer cardiovascular side effects, although it has some ejaculatory side effects. The nonsubtype selective agent alfuzosin also demonstrates efficacy and offers an enhanced side effect profile, particularly minimizing hypotension. Other agents with super selective specificity for the alpha1aAR subtype are under investigation. CONCLUSIONS Further advances in the treatment of LUTS associated with BPH may depend not only on receptor subtype selectivity, but also on other pharmacokinetic and pharmacodynamic factors.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D011470	Prostatic Hyperplasia	Increase in constituent cells in the PROSTATE, leading to enlargement of the organ (hypertrophy) and adverse impact on the lower urinary tract function. This can be caused by increased rate of cell proliferation, reduced rate of cell death, or both.	Adenoma, Prostatic,Benign Prostatic Hyperplasia,Prostatic Adenoma,Prostatic Hyperplasia, Benign,Prostatic Hypertrophy,Prostatic Hypertrophy, Benign,Adenomas, Prostatic,Benign Prostatic Hyperplasias,Benign Prostatic Hypertrophy,Hyperplasia, Benign Prostatic,Hyperplasia, Prostatic,Hyperplasias, Benign Prostatic,Hypertrophies, Prostatic,Hypertrophy, Benign Prostatic,Hypertrophy, Prostatic,Prostatic Adenomas,Prostatic Hyperplasias, Benign,Prostatic Hypertrophies
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014555	Urination Disorders	Abnormalities in the process of URINE voiding, including bladder control, frequency of URINATION, as well as the volume and composition of URINE.	Disorder, Urination,Disorders, Urination,Urination Disorder
D058668	Adrenergic alpha-1 Receptor Antagonists	Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.	Adrenergic alpha-1 Antagonists,Adrenergic alpha-1 Receptor Blockers,Adrenergic alpha1-Antagonists,alpha-1 Adrenergic Blocking Agents,alpha1-Adrenergic Antagonists,alpha1-Adrenoceptor Blocker,Adrenergic alpha 1 Antagonists,Adrenergic alpha 1 Receptor Antagonists,Adrenergic alpha 1 Receptor Blockers,Adrenergic alpha1 Antagonists,Antagonists, alpha1-Adrenergic,alpha 1 Adrenergic Blocking Agents,alpha-1 Antagonists, Adrenergic,alpha1 Adrenergic Antagonists,alpha1 Adrenoceptor Blocker,alpha1-Antagonists, Adrenergic
D018340	Receptors, Adrenergic, alpha-1	A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.	Adrenergic alpha-1 Receptors,Receptors, alpha-1 Adrenergic,alpha-1 Adrenergic Receptors,Adrenergic Receptor, alpha-1,Adrenergic alpha-1A Receptors,Adrenergic alpha-1B Receptors,Adrenergic alpha-1D Receptors,Receptor, Adrenergic, alpha-1,Receptor, Adrenergic, alpha-1A,Receptor, Adrenergic, alpha-1B,Receptor, Adrenergic, alpha-1D,Receptors, Adrenergic, alpha-1A,Receptors, Adrenergic, alpha-1B,Receptors, Adrenergic, alpha-1D,alpha 1 Adrenergic Receptor,alpha-1A Adrenergic Receptor,alpha-1B Adrenergic Receptor,alpha-1C Adrenergic Receptor,alpha-1D Adrenergic Receptor,Adrenergic Receptor, alpha 1,Adrenergic Receptor, alpha-1A,Adrenergic Receptor, alpha-1B,Adrenergic Receptor, alpha-1C,Adrenergic Receptor, alpha-1D,Adrenergic Receptors, alpha-1,Adrenergic alpha 1 Receptors,Adrenergic alpha 1A Receptors,Adrenergic alpha 1B Receptors,Adrenergic alpha 1D Receptors,Receptor, alpha-1 Adrenergic,Receptor, alpha-1A Adrenergic,Receptor, alpha-1B Adrenergic,Receptor, alpha-1C Adrenergic,Receptor, alpha-1D Adrenergic,Receptors, Adrenergic alpha-1,Receptors, Adrenergic alpha-1A,Receptors, Adrenergic alpha-1B,Receptors, Adrenergic alpha-1D,Receptors, alpha 1 Adrenergic,alpha 1 Adrenergic Receptors,alpha 1A Adrenergic Receptor,alpha 1B Adrenergic Receptor,alpha 1C Adrenergic Receptor,alpha 1D Adrenergic Receptor,alpha-1 Adrenergic Receptor,alpha-1 Receptors, Adrenergic,alpha-1A Receptors, Adrenergic,alpha-1B Receptors, Adrenergic,alpha-1D Receptors, Adrenergic