title: Characterization of a novel alpha 1-adrenoceptor antagonist, SGB-1534, in contractile response of isolated canine arterial and venous smooth muscle to exogenous noradrenaline: comparison with prazosin, phentolamine and yohimbine.
abstract: The pharmacological properties of SGB-1534, 3-[2-[4-[(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4(1H,3H)- quinazolinedione monohydrochloride, a selective alpha 1-adrenoceptor antagonist, compared with prazosin, phentolamine and yohimbine, were examined in contractile responses of isolated canine mesenteric arteries and veins and femoral arteries and veins to exogenous noradrenaline. The arteries and veins concentration-dependently contracted when exposed to noradrenaline. The sensitivity to noradrenaline, when compared in terms of pD2 values, was significantly higher in the veins than in the arteries. Phentolamine and yohimbine were competitive antagonists against noradrenaline in the arteries and the veins. SGB-1534 and prazosin caused a parallel shift to the right of the concentration-response curves for noradrenaline only in the arteries: the two antagonists were less effective in the veins than in the arteries when low concentrations of noradrenaline were applied. The pharmacological characteristics of SGB-1534 resemble those of prazosin. The pA2 values for SGB-1534 against noradrenaline in the arteries were much higher than those for prazosin, phentolamine and yohimbine. The result indicates that SGB-1534 may predominantly act upon arterial resistance vessels rather than the venous side, resulting in potent hypotension.
authors.affiliation: Department of Pharmacology, Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koga
authors.forename: Y
authors.initials: Y
authors.lastname: Shiraki
authors.forename: K
authors.initials: K
authors.lastname: Sakai
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D015016:Yohimbine; C042712:SGB 1534; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine