Abstract:
:Alpha1-adrenoceptor antagonists have been shown to decrease both the voiding and storage symptoms of benign prostatic hyperplasia (BPH). Based on the assumption that these symptoms can be attributed to the consequences of the increase in outflow resistance caused by noradrenaline stimulation of stromal alpha1-adrenoceptors in the enlarged prostate, prostatic alpha1-adrenoceptors have become a target for therapeutic interventions. In some patients, alpha1-adrenoceptor antagonists in common clinical use produce intolerable side effects which may be attributed to action on non-prostatic alpha1-adrenoceptors. Therefore, attempts have been made to find alpha1-adrenoceptor antagonists that have selective effects on the prostate ('uroselective' agents), to maintain efficacy in uroflow and eliminate adverse effects. The term uroselectivity has been used in various contexts, but drugs may be discussed as uroselective from a receptor pharmacological, physiological, or clinical perspective. Provided that the alpha1-adrenoceptor subtype in the prostate, bladder neck and urethra is uniform, unique, and cannot be found in other parts of the body, drugs with selectivity for this receptor could be called uroselective. However, available evidence suggests that (1) more than one alpha1-adrenoceptor subtype can be found in the lower urinary tract, and that the main alpha1-adrenoceptor mediating contraction still remains to be definitely defined; (2) the receptor(s) is (are) most probably not unique to the lower urinary tract, and (3) alpha1-adrenoceptor sites outside the prostate (with still undefined subtypes) may contribute to the lower urinary tract symptoms of BPH. Therefore, it does not seem possible to define uroselectivity in terms of selectivity for the alpha1-adrenoceptor(s) occurring in the prostate. Several animal models have been developed where the potency order of effects of various alpha1-adrenoceptor antagonists on blood pressure and urethral pressure have been measured simultaneously. Such models can be useful when screening drugs that may be developed for therapeutic use, but they also have limitations, since side effects that may be dose limiting clinically are not always related to a decrease in blood pressure. Certainly, a drug may be said to have physiological or functional uroselectivity if it lowers outflow resistance more effectively than it affects other defined physiological functions. A clinically meaningful definition of uroselectivity can only be made in man and considers desired effects on obstruction and lower urinary tract symptoms relative to adverse effects.
journal_name
Eur Uroljournal_title
European urologyauthors
Andersson KEdoi
10.1159/000052228subject
Has Abstractpub_date
1998-01-01 00:00:00pages
7-11eissn
0302-2838issn
1873-7560pii
eur3b007journal_volume
33 Suppl 2pub_type
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