Antihypertensive effects of CS-905, a novel dihydropyridine Ca++ channel blocker.
CS-905 is a novel dihydropyridine calcium blocker. A single oral administration of CS-905 or nicardipine at doses of 0.3-3.0 mg/kg produced a dose-dependent reduction of blood pressure in conscious SHR. CS-905, when administered orally in conscious SHR, was more than 3 times as potent as nicardipine. Unlike the hypotensive effect of nicardipine, that of CS-905 has a gradual onset and is long-lasting, with little increase in heart rate. An intravenous administration of CS-905 also produced a hypotension with a slow onset and long duration in SHR, but CS-905 was 3 times less potent than nicardipine by intravenous administration. This difference may be attributed to the first pass effect, which was associated with nicardipine but not with CS-905. The blood pressure lowering effects of CS-905 was most potent in DOCA-salt hypertensive rats, followed by SHR, RHR and normotensive rats, in this order. CS-905 is expected to be an antihypertensive agent that is effective on a once a day regimen in clinical settings.
Oizumi
K
K
Sankyo Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Nishino
H
H
Koike
H
H
Sada
T
T
Miyamoto
M
M
Kimura
T
T
D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents; D001011:Aorta / Q000187:drug effects; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003900:Desoxycorticosterone; D004095:Dihydropyridines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009392:Nephrectomy; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D001385:Azetines; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D003900:Desoxycorticosterone; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine