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The concept of uroselectivity

K E Andersson1

  • 1Department of Clinical Pharmacology, Lund University Hospital, Sweden. ka3x@virginia.edu

European Urology
|April 29, 1998
PubMed
Summary

Alpha1-adrenoceptor antagonists treat benign prostatic hyperplasia (BPH) symptoms by targeting prostate receptors. However, achieving true uroselectivity is complex due to varied receptor subtypes and locations, necessitating clinical evaluation for efficacy and safety.

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Area of Science:

  • Pharmacology
  • Urology
  • Drug Discovery

Background:

  • Alpha1-adrenoceptor antagonists are used to treat benign prostatic hyperplasia (BPH) symptoms.
  • These drugs target noradrenaline stimulation of alpha1-adrenoceptors in the enlarged prostate to reduce outflow resistance.
  • Intolerable side effects from non-selective antagonists necessitate the development of 'uroselective' agents.

Purpose of the Study:

  • To explore the concept and definition of uroselectivity for alpha1-adrenoceptor antagonists.
  • To evaluate the feasibility of defining uroselectivity based on prostate-specific receptor subtypes.
  • To discuss the limitations of preclinical models and the importance of clinical assessment for uroselectivity.

Main Methods:

  • Review of existing evidence on alpha1-adrenoceptor subtypes in the lower urinary tract.
  • Analysis of animal models used to assess drug selectivity for blood pressure versus urethral pressure.
  • Consideration of pharmacological, physiological, and clinical perspectives of uroselectivity.

Main Results:

  • Evidence suggests multiple alpha1-adrenoceptor subtypes exist in the lower urinary tract, and their precise role in BPH contraction is not fully defined.
  • Alpha1-adrenoceptors are not unique to the prostate, and extraprostatic sites may contribute to BPH symptoms.
  • Preclinical models have limitations in predicting clinical side effects, as dose-limiting adverse events are not always linked to blood pressure changes.

Conclusions:

  • Defining uroselectivity based solely on selectivity for prostate alpha1-adrenoceptors is currently not feasible.
  • Physiological or functional uroselectivity can be defined by comparing effects on outflow resistance versus other physiological functions.
  • A clinically meaningful definition of uroselectivity requires human trials assessing therapeutic effects against adverse events.

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