Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in conscious, renal-hypertensive dogs.
The antihypertensive action of (+/-)-(R*)-2,6-dimethyl-4- (m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was evaluated in conscious, renal-hypertensive dogs. When KW-3049 (0.1, 0.3 and 1 mg/kg) was orally administered, antihypertensive action and increased heart rate with peak time after 60 to 120 min of administration were observed, and the duration of actions at the dose of 0.3 mg/kg (p.o.) or more lasted for more than 7 h. When nifedipine (0.3 and 1 mg/kg) and nicardipine (1 and 3 mg/kg) were orally given, the duration of antihypertensive action was shorter. Nitrendipine (1 and 3 mg/kg p.o.) showed antihypertensive action and increased heart rate with peak time after 45 to 60 min of administration, and the duration of action at 3 mg/kg (p.o.) lasted for 7 h or longer. The antihypertensive activity of KW-3049 at the action peak was 6.1, 12.1 and 8.9 fold as compared with those of nifedipine, nicardipine and nitrendipine, respectively. Also, when KW-3049 at 0.3 mg/kg (p.o.) was administered after 1 h of propranolol (20 mg/kg p.o.) administration, the increase of the heart rate was markedly inhibited while its antihypertensive action remained unchanged. From these results, it was demonstrated that KW-3049 shows potent and long-lasting antihypertensive action with gradual appearance of action, and was suggested that it may be an useful antihypertensive agent.
Karasawa
A
A
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Ikeda
J
J
Yamada
K
K
Kubo
K
K
Oka
T
T
Nakamizo
N
N
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006977:Hypertension, Renal / Q000188:drug therapy*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology / Q000627:therapeutic use; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009568:Nitrendipine / Q000494:pharmacology / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009568:Nitrendipine; D011433:Propranolol; D009529:Nicardipine; D009543:Nifedipine