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Z-350, a new chimera compound possessing α1-adrenoceptor antagonistic and steroid 5α-reductase inhibitory actions.
- Source :
- Naunyn-Schmiedeberg's Archives of Pharmacology; Jun1999, Vol. 359 Issue 6, p433-438, 6p
- Publication Year :
- 1999
-
Abstract
- The effects of Z-350, (S)-4-[3-(4-{1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy} benzoyl)indole-1-yl]butyric acid hydrochloride, a newly synthesized compound possessing α<subscript>1</subscript>-adrenoceptor antagonistic and steroid 5α-reductase inhibitory actions, were studied in vitro. In functional experiments, Z-350 shifted the concentration/response curve for the phenylephrine-induced contraction of rabbit prostate, urethra and aorta to the right with pA<subscript>2</subscript> values of 8.04, 7.57 and 7.13, respectively. The binding affinity of Z-350 for α<subscript>1</subscript>-adrenoceptors in rabbit prostate, urethra and aorta were estimated by the displacement of [<superscript>3</superscript>H]prazosin. The p K <subscript>i</subscript> values for this action of Z-350 were 7.53, 7.95 and 7.62 for the prostate, urethra and aorta, respectively. α<subscript>1</subscript>-Adrenoceptor subtype selectivities were studied in the submaxillary gland (α<subscript>1A</subscript>) and liver (α<subscript>1B</subscript>) of rat. Z-350 inhibited the specific binding of [<superscript>3</superscript>H]prazosin to α<subscript>1A</subscript> and α<subscript>1B</subscript>-adrenoceptors with p K <subscript>i</subscript> values of 7.82 and 7.29, respectively. Z-350 inhibited rat prostatic steroid 5α-reductase non-competitively with a pIC<subscript>50</subscript> of 8.42. These results indicate that Z-350 is a α<subscript>1</subscript>-adrenoceptor antagonist and is a steroid 5α-reductase inhibitor. It is expected that Z-350 will be a candidate drug for the treatment of benign prostatic hyperplasia. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00281298
- Volume :
- 359
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Naunyn-Schmiedeberg's Archives of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 49984279
- Full Text :
- https://doi.org/10.1007/PL00005372