Jpn. J. Pharmacol. 79 (4), 447-454 (1999)

Naftopidil, a Novel alpha₁-Adrenoceptor Antagonist, Displays Selective Inhibition of Canine Prostatic Pressure and High Affinity Binding to Cloned Human alpha₁-Adrenoceptors

Ryo-ich Takei (1), Ichiro Ikegaki (1,*), Katsushi Shibata (2), Gozoh Tsujimoto (2) and Toshio Asano (1)


(1) Laboratory for Pharmacology, Institute for Life Science Research, Asahi Chemical Industry, 632-1 Mifuku, Ohito-cho, Tagata-gun, Shizuoka 410-2321, Japan
(2) Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-0004, Japan
(*) To whom correspondence should be addressed.

Abstract: The pharmacological profiles of the alpha₁-adrenoceptor antagonists naftopidil, tamsulosin and prazosin were studied in an anesthetized dog model that allowed the simultaneous assessment of their antagonist potency against phenylephrine-mediated increases in prostatic pressure and mean blood pressure. The intravenous administration of each of these compounds dose-dependently inhibited phenylephrine-induced increases in prostatic pressure and mean blood pressure. To further assess the ability of the three compounds to inhibit phenylephrine-induced responses, the doses required to produce a 50% inhibition of the phenylephrine-induced increases in prostatic and mean blood pressure and the selectivity index obtained from the ratio of those two doses were determined for each test compound. Forty minutes after the intravenous administration of naftopidil, the selectivity index was 3.76, and those of tamsulosin and prazosin were 1.23 and 0.61, respectively. These findings demonstrated that naftopidil selectively inhibited the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure in the anesthetized dog model. The selectivity of naftopidil for prostatic pressure was the most potent among the test compounds. In addition, using cloned human alpha₁-adrenoceptor subtypes, naftopidil was selective for the alpha_1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha_1a- and alpha_1b-adrenoceptor subtypes, respectively. The selectivity of naftopidil for prostatic pressure may be attributable to its high binding affinity for alpha_1a- and alpha_1d-adrenoceptor subtypes.

Keywords: Naftopidil, alpha₁-Adrenoceptor antagonist, Prostate pressure, Benign prostatic hyperplasia, Anesthetized dog