ISSN:
1432-1912
Keywords:
Key words Z-350
;
α1-Adrenoceptors
;
Steroid
;
5α-reductase
;
Lower urinary tract
;
Benign prostatic
;
hyperplasia
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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 α1-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 pA2 values of 8.04, 7.57 and 7.13, respectively. The binding affinity of Z-350 for α1-adrenoceptors in rabbit prostate, urethra and aorta were estimated by the displacement of [3H]prazosin. The pK i values for this action of Z-350 were 7.53, 7.95 and 7.62 for the prostate, urethra and aorta, respectively. α1-Adrenoceptor subtype selectivities were studied in the submaxillary gland (α1A) and liver (α1B) of rat. Z-350 inhibited the specific binding of [3H]prazosin to α1A and α1B-adrenoceptors with pK i values of 7.82 and 7.29, respectively. Z-350 inhibited rat prostatic steroid 5α-reductase non-competitively with a pIC50 of 8.42. These results indicate that Z-350 is a α1-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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00005372
Permalink
