The first clinical evidence for the utility of an a-adrenoceptor antagonist in the symptomatic treatment of benign prostatic hyperplasia (BPH) was provided by Caine and colleagues (52) using phenoxybenzamine, an irreversible antagonist that alkylates both a1- and a2-adrenoceptor adrenoceptors. The efficacy of phenoxybenzamine has been confirmed in several subsequent studies (53,54), and the intravenous administration of a nonselective a-adrenoceptor antagonist, phentolamine, was shown to relieve the acute urinary retention associated with BPH (55), thereby supporting the notion that an a-adrenoceptor antagonist would be useful in the treatment of BPH. In spite of the fact that nonselective a-adrenoceptor antagonists have been shown to relieve symptoms associated with BPH, because the contractile response of isolated prostatic smooth muscle is mediated by aradrenoceptors (56), the design of drugs for this indication has recently concentrated on selective aradrenoceptor antagonists. Most of the currently marketed drugs are quinazolines, which have a high degree of selectivity for ar versus a2-adrenoceptors (i.e., prazosin, terazosin, doxazosin, alfuzosin, bunazosin). Although these drugs are generally believed to produce fewer side effects than phenoxybenzamine (54), this has not been demonstrated conclusively in side-by-side comparative studies.
More recent data with naftopidil, an antagonist having high affinity for a2-adrenoceptors in some assays (6,57,58), suggest that the drug is efficacious in the treatment of BPH without producing unacceptable side effects (59). As such, the possibility exists that blockade of a2-adrenoceptors may be a desirable feature in an a-adrenoceptor antagonist used for the treatment of BPH.
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