Effects of the new calcium antagonist benidipine hydrochloride on cardiohemodynamics in anesthetized dogs.
The effects of (+/-)-(R*)-2,6-dimethyl-4-(m-nitro-phenyl)-1,4-dihydropyridine -3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinylester, methylester hydrochloride (benidipine hydrochloride, KW-3049) on the cardiohemodynamics were investigated in open-chest, anesthetized dogs, in comparison with those of nifedipine. When KW-3049 at a dose of 3 micrograms/kg was intravenously administered, hypotensive action (delta dBP = -20 mmHg) with a peak attained 3 to 5 min after the administration was observed and its action lasted for 2 h or more. Simultaneously, a slight decrease of heart rate and continuous increases of LV max dp/dt and cardiac output were recognized. At the administration with 10 micrograms/kg i.v., hypotensive action (delta dBP = -35 mmHg) with a peak 3 min after the administration appeared and continued for 3 h or more. At this time, continuous decrease of heart rate by about 18% and continuous increase of cardiac output were observed. The LV max dp/dt transiently decreased and then turned to increase, and the cardiac work was continuously decreased. When nifedipine at doses of 10 or 50 micrograms/kg was intravenously administered, hypotensive action (delta dBP = -31 and -52 mmHg) with a peak attained 1 min after the administration was observed and its action rapidly began to recover. At the administration with 50 micrograms/kg i.v., the heart rate was slightly decreased (10%). The LV max dp/dt was transiently reduced by 18% at 10 micrograms/kg i.v. and by 45% at 50 micrograms/kg i.v., respectively, and the augmented cardiac output lasted for 30 to 60 min. At the administration of 50 micrograms/kg i.v., cardiac work was continuously decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Karasawa
A
A
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Shizuoka, Japan.
Kubo
K
K
Oka
T
T
Nakamizo
N
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects
D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009543:Nifedipine