Naftopidil, a Novel α1-Adrenoceptor Antagonist, Displays Selective Inhibition of Canine Prostatic Pressure and High Affinity Binding to Cloned Human α1-Adrenoceptors
Open Access
- 1 January 1999
- journal article
- Published by Elsevier BV in The Japanese Journal of Pharmacology
- Vol. 79 (4), 447-454
- https://doi.org/10.1254/jjp.79.447
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 alpha1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha1a- and alpha1b-adrenoceptor subtypes, respectively. The selectivity of naftopidil for prostatic pressure may be attributable to its high binding affinity for alpha1a- and alpha1d-adrenoceptor subtypes.Keywords
This publication has 23 references indexed in Scilit:
- Cloning, functional expression and tissue distribution of human α1C‐adrenoceptor splice variantsFEBS Letters, 1995
- Use of recombinant α1-adrenoceptors to characterize subtype selectivity of drugs for the treatment of prostatic hypertrophyEuropean Journal of Pharmacology: Molecular Pharmacology, 1995
- The pharmacological profile of cloned and stably expressed α1B-adrenoceptor in CHO cellsEuropean Journal of Pharmacology: Molecular Pharmacology, 1994
- Effect of naftopidil on urethral obstruction in benign prostatic hyperplasia: Assessment by urodynamic studiesThe Prostate, 1994
- Cloning, Functional Expression and Tissue Distribution of Human cDNA for the α1C-Adrenergic ReceptorBiochemical and Biophysical Research Communications, 1993
- AlfuzosinDrugs, 1993
- Binding characteristics of naftopidil and α1-adrenoceptor antagonists to prostatic α-adrenoceptors in benign prostatic hypertrophyLife Sciences, 1992
- Prazosin in the Treatment of Prostatic Obstruction A Placebo‐controlled StudyBritish Journal of Urology, 1987
- In vitro characterization of the α-adrenoceptors in human prostateEuropean Journal of Pharmacology, 1985
- A Neurohistochemical and Histological Study of Peripheral Autonomic Neurons of the Human Bladder Neck and ProstateUrologia Internationalis, 1977