title: Alpha-1 adrenoceptor antagonist effects of the optical isomers of YM-12617 in rabbit lower urinary tract and prostate.
abstract: The alpha-1 adrenoceptor antagonist effects of the optical isomers of YM-12617 (5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]- 2-methoxybenzenesulfonamide HCl), a potent and selective alpha-1 adrenoceptor antagonist, were evaluated in the rabbit lower urinary tract and prostate. R-(-)-YM-12617 (1 X 10(-10) to 3 X 10(-9) M) and S-(+)-YM-12617 (3 X 10(-8) to 3 X 10(-7) M) antagonized phenylephrine-induced contraction in a competitive manner in the urinary bladder base (trigone), proximal urethra and prostate. The mean pA2 value for R-(-)-YM-12617 at the alpha-1 adrenoceptor of trigone, urethra and prostate was 9.91, 9.62 and 9.92, respectively, and that for S-(+)-YM-12617 was 8.09, 7.92 and 7.77, respectively. Therefore, R-(-)-YM-12617 is a 50 to 141 times more potent antagonist than S-(+)-YM-12617 at the alpha-1 adrenoceptor in these tissues. The present results also indicate that the alpha-1 adrenoceptor in the lower urinary tract and prostate can distinguish clearly between the optical isomers of YM-12617. Similar results were obtained in the aorta of rabbits in which a dramatic stereochemical preference of R-(-)-YM-12617 for the alpha-1 adrenoceptor also exists.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007536:Isomerism; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects*; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D014521:Urethra / Q000187:drug effects; D014551:Urinary Tract / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects; D000096926:Benzenesulfonamides
chemical_list: D000317:Adrenergic alpha-Antagonists; D010656:Phenylephrine; D013449:Sulfonamides; C044648:YM 12617; D000096926:Benzenesulfonamides