Abstract
Naftopidil, a phenylpiperazine derivative, is a novel α1-adrenoceptor antagonist and is new drug for the bladder outlet obstruction in patients with benign prostatic hyperplasia (BPH). Naftopidil competitively inhibited specific [3H] prazosin binding in prostatic membranes of humans, and its Ki value was 11.6 nM. Using cloned human α1-adrenoceptor subtypes (α1a, α1b and α1d), naftopidil was selective for the α1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the α1a- and α1b-adrenoceptor subtypes, respectively. In anesthetized dogs, naftopidil selectively inhibited the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure. The selectivity of naftopidil for prostatic pressure was more potent than those of tamsulosin and prazosin. In conscious rabbits, the effect of naftopidil on the blood pressure reactions following the tilting was less potent than those of tamsulosin and prazosin. In clinical studies, naftopidil has been demonstrated to be effective in the treatment of bladder outlet obstruction in patients with BPH. In Japan, naftopidil has been already approved for clinical use as a drug for BPH.
