[Antihypertensive effect of felodipine, a new calcium antagonist].
The antihypertensive effect of felodipine was examined in various hypertensive animal models. In spontaneously hypertensive rats, felodipine administered singly at 0.1-1.0 mg/kg (p.o.) had a dose-dependent antihypertensive effect. Nifedipine was effective at 1 mg/kg. In the repeated oral administration experiment, both the maximum decrease in blood pressure and duration of the effect increased gradually and reached steady levels at 3 weeks of administration, which were maintained thereafter. Similar results were noted with nifedipine, but felodipine was longer-acting (4-6 hr) in the steady state than nifedipine (1-2 hr). No development of tolerance was observed during the administration period. In DOCA-salt and renal hypertensive (2K1C) rats, felodipine at 0.1-0.5 mg/kg (p.o.) was superior to nifedipine in the maximum decrease in blood pressure and duration of the effect. Felodipine up to 1 mg/kg (p.o.) caused no significant heart rate increase in any rat model. In renal hypertensive (2K2C) dogs given felodipine at 0.2-0.5 mg/kg (p.o.), the effect lasted for 2 hr after injection. This felodipine effect was stronger and longer lasting than the nifedipine one. At 0.5 mg/kg of felodipine, the heart rate was transiently increased. The present results show that felodipine has a stronger and long-lasting antihypertensive effect than nifedipine in the hypertension models.
Inoue
T
T
Pharma Research Laboratories, Hoechst Japan Ltd., Saitama.
Omosu
M
M
Hayashi
S
S
Sakaguchi
S
S
Nakao
K
K
Inukai
T
T
Odagiri
N
N
Ono
T
T
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015736:Felodipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D006978:Hypertension, Renovascular / Q000188:drug therapy; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015736:Felodipine