title: KMD-3213, a novel alpha1A-adrenoceptor antagonist, potently inhibits the functional alpha1-adrenoceptor in human prostate.
abstract: KMD-3213, (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phe noxy]ethyl]amino]propyl]indoline-7-carboxamide, is a novel and selective alpha1A-adrenoceptor antagonist. The potency of this drug to antagonize functional alpha1-adrenoceptor-mediated contraction in human prostatic smooth muscle was evaluated and compared with that of other alpha1-adrenoceptor antagonists. KMD-3213 inhibited noradrenaline-induced contractions with an apparent pK(B) value of 9.45 +/- 0.039, indicating a potency similar to that of tamsulosin. The affinity of prazosin for prostatic alpha1-adrenoceptors is given as potency for the alpha1L-adrenoceptor with an estimated pA2 value of 8.84 +/- 0.044. The data obtained in this study suggest that KMD-3213, an alpha1A-adrenoceptor-selective antagonist, has strong affinity for the alpha1L-adrenoceptor in the human prostate.
authors.affiliation: Department of Urology, Faculty of Medicine, The University of Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Moriyama
authors.forename: K
authors.initials: K
authors.lastname: Akiyama
authors.forename: S
authors.initials: S
authors.lastname: Murata
authors.forename: J
authors.initials: J
authors.lastname: Taniguchi
authors.forename: N
authors.initials: N
authors.lastname: Ishida
authors.forename: S
authors.initials: S
authors.lastname: Yamazaki
authors.forename: K
authors.initials: K
authors.lastname: Kawabe
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000503:physiopathology / Q000628:therapy; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; C095285:silodosin; D000077409:Tamsulosin; D009638:Norepinephrine; D011224:Prazosin