Drugs for treatment of benign prostatic hyperplasia: Affinity comparison at cloned alpha(1)-adrenoceptor subtypes and in human prostate

1 We have previously shown that among alpha(1)-adrenoceptor antagonists used or investigated for the treatment of benign prostatic hyperplasia, tamsulosin discriminates alpha(1)-adrenoceptor subtypes in rat tissues whereas alfuzosin and naftopidil do not. We now expand these studies to additional drugs (doxazosin, terazosin) being used and/or investigated for this purpose, and have evaluated all of these drugs at cloned subtypes and in human prostate. 2 Competition binding studies were performed with [H-3]-prazosin in membrane samples from rat spleen, kidney and cerebral cortex and human prostate and with cloned alpha(1)-adrenoceptors expressed in COS cells. Doxazosin and terazosin did not discriminate alpha(1)-adrenoceptor subtypes in rat kidney and cerebral cortex. In contrast, the subtypes present in the tissues were well discriminated by the alpha(1A)-adrenoceptor-selective reference drug WE 4101. 3 Alfuzosin, doxazosin, naftopidil and terazosin did not discriminate cloned alpha(1)-adrenoceptor subtypes transiently expressed in COS cells whereas tamsulosin and WE 4101 did. 4 In human prostate, alfuzosin, doxazosin, naftopidil and terazosin did not discriminate the alpha(1A)-adrenoceptor subtypes present in this tissue whereas tamsulosin and the alpha(1A)-adrenoceptor-selective reference drugs WE 4101, phentolamine and 5-methylurapidil did. Based on data with the alpha(1A)-adrenoceptor-selective drugs, human prostate contains alpha(1A)- and alpha(1B)-adrenoceptors in an approximate 70:30% ratio. 5 We conclude that tamsulosin, in common with WE 4101, but in contrast to alfuzosin, doxazosin, naftopidil, and terazosin is selective for alpha(1A)-adrenoceptors which appear to dominate in the human prostate; the therapeutic relevance of this selectivity remains to be assessed in clinical studies.