Purpose: We provide a comprehensive overview of the role of α 1-adrenergic receptors (α1ARs) as critical mediators of lower urinary tract symptoms (LUTS) and pathophysiology in benign prostatic hyperplasia (BPH), and we review the pharmacological antagonists of α1ARs. Materials and Methods: A review was performed of pertinent studies in the literature relating to the pathophysiology of LUTS and BPH, focusing on the role of α1ARs, and of clinical trial and practice data evaluating the different agents that inhibit these receptors. Results: Further characterization of the α1AR 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 α1aAR and α1dAR subtypes appears to be a common feature in symptomatic BPH and α1aARs are enriched in prostatic tissue, drugs that demonstrate high α 1aAR selectivity have attracted attention. Tamsulosin, which has high affinity for α1aAR and α1dAR subtypes but not for α1bAR, 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 α1aAR 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.
- Prostatic hyperplasia, urinary tract
- Receptors, adrenergic, alpha
ASJC Scopus subject areas