title: Cardiohemodynamic effect of a novel calcium antagonist, SD-3211, in the dog.
abstract: The cardiohemodynamic effects of SD-3211, a calcium antagonist possessing a unique structure, were studied in anesthetized open-chest dogs and in conscious dogs. SD-3211 (10-300 micrograms/kg, i.v.) increased coronary and vertebral artery blood flow dose-dependently while lowering blood pressure, indicating a vasodilatation of these arteries. SD-3211 caused a significant increase in heart rate at 10-100 micrograms/kg, but a significant decrease at 300 micrograms/kg. Left ventricular dp dtmax was dose-dependently decreased at the dose range examined, and the change was significant at 300 micrograms/kg. When compared with the cardiohemodynamic effects of diltiazem (10 300 micrograms/kg, i.v.) and nicardipine (1-30 micrograms/kg, i.v.), the selectivity of SD-3211 with regard to vasodilatation as compared to cardiac depression, manifested by a reduction in heart rate and myocardial contractility, was greater than that of diltiazem, but less than that of nicardipine. Furthermore, a comparative study of the effects of orally administered SD-3211 and diltiazem on blood pressure and atrioventricular conduction in conscious, normotensive dogs, demonstrated that SD-3211 had a more potent and long-lasting hypotensive effect, but a much weaker effect on atrioventricular conduction prolongation than diltiazem. Thus, these in vivo cardiohemodynamic studies show that SD-3211 possesses a tissue-selectivity for vasculature, respectively cardiac tissues, which is intermediate between diltiazem and nicardipine.
authors.affiliation: Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takada
authors.forename: N
authors.initials: N
authors.lastname: Miyawaki
authors.forename: K
authors.initials: K
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: K
authors.initials: K
authors.lastname: Matsuno
authors.forename: N
authors.initials: N
authors.lastname: Ishida
authors.forename: H
authors.initials: H
authors.lastname: Yamauchi
authors.forename: T
authors.initials: T
authors.lastname: Iso
mesh_terms: D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D013844:Thiazoles; D009529:Nicardipine; C064356:sesamodil; D004110:Diltiazem