FUNCTIONAL UROSELECTIVITY

alpha(1)-Adrenoceptors mediating sympathetic tone to smooth muscle cel ls are located within the prostatic tissue, bladder base and in the pr oximal urethra, but are also widely distributed within a large number of tissues, especially the vascular beds and the central nervous syste m. Compounds clinically used in the symptomatic treatment of benign pr ostatic hyperplasia must therefore exhibit functional uroselectivity. This means that they should preferentially act on the lower urinary tr act rather than the vasculature or central nervous system. Few clinica lly used alpha(1)-adrenoceptor antagonists show selectivity for the al pha(2a/A)-adrenoceptor subtype, whereas most of them have similar affi nities for the three cloned subtypes (alpha(1a)-, alpha(1b)- and alpha (1d)-adrenoceptors). Recent data from in vitro studies assessing pharm acological uroselectivity and from in vivo models evaluating functiona l uroselectivity challenged the relevance of the affinity or the selec tivity for a known alpha(1)-adrenoceptor subtype in predicting functio nal uroselectivity. They suggest instead that another subtype, like th e alpha(1L)-adrenoceptor, might be functionally involved. In conclusio n, the actual state of knowledge on alpha(1)-adrenoceptor subtype dist ribution and function, does not support a role of pharmacological uros electivity in predicting functional uroselectivity. Furthermore, funct ional uroselectivity can be achieved in the absence of selectivity for the alpha(1)-adrenoceptor subtypes described so far.