Cardiovascular effects of a new 1,5-benzothiazepine calcium antagonist in anesthetized dogs.
Cardiovascular effects of TA-3090 ((+)(2S,3S)-3-acetoxy-8-chloro-5-(2-(dimethylamino)ethyl)-2, 3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4-(5H)-one maleate), a new 1,5-benzothiazepine derivative, were studied in pentobarbital anesthetized dogs. TA-3090 administered intraarterially (i.a.) was 3 times more potent than diltiazem in increasing vertebral and coronary blood flows. In the autoperfused preparation, TA-3090 i.a. exhibited weak negative inotropic effect as compared with its coronary vasodilating effect; negative inotropy was less than 10% at a dose which increased coronary blood flow by 50%. The selectivity of TA-3090 for coronary artery was greater than that of verapamil. Intravenous administration of TA-3090 (0.025-0.2 mg/kg) produced increases in cardiac output and arterial, especially vertebral and coronary blood flow as well as in left ventricular dp/dtmax. The increasing effect in blood flow was most prominent in the vertebral artery. Upon intraduodenal administration of 2 and 5 mg/kg TA-3090, the increases in vertebral and coronary blood flow lasted for more than 2-5 h; the effect of TA-3090 on vertebral blood flow was approximately twice as potent as that of diltiazem. Thus, TA-3090 could be demonstrated to possess potent and long-lasting vasodilating activity with selectivity for vertebral and coronary arteries, exerting however, weak negative inotropic effect.
Murata
S
S
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Kikkawa
K
K
Yabana
H
H
Nagao
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004110:Diltiazem / Q000031:analogs & derivatives*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013841:Thiazepines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D013841:Thiazepines; C056595:clentiazem; D004110:Diltiazem