A novel nonpeptidic, orally active renin inhibitor.
BW-175 is a newly synthesized renin inhibitor which is a nonpeptidic, norleucine analog. Its IC50 values for renin activity in human, squirrel monkey, marmoset, dog, hog, rabbit and rat plasma were 3.3, 6.6, 2.4, 42, 110, 86 and 3500 nM, respectively, and 26 microM for cathepsin D. Pepsin and angiotensin converting enzyme were hardly inhibited at 10(-4) M. BW-175 showed an oral bioavailability of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. In normotensive, furosemide-treated high-renin marmosets, BW-175 (30 mg/kg p.o.) caused an intensive reduction in plasma renin activity and plasma angiotensin I formation, associated with a reduction in systolic blood pressure of 10-20 mm Hg for 2 hours.
Morishima
H
H
Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Koike
Y
Y
Nakano
M
M
Atsuumi
S
S
Tanaka
S
S
Funabashi
H
H
Hashimoto
J
J
Sawasaki
Y
Y
Mino
N
N
Nakano
M
M
D000614:Aminocaproates / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D002143:Callitrichinae; D002402:Cathepsin D / Q000037:antagonists & inhibitors; D002417:Cattle; D004285:Dogs; D005665:Furosemide / Q000494:pharmacology; D005750:Gastric Juice / Q000201:enzymology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009025:Morpholines / Q000493:pharmacokinetics / Q000494:pharmacology*; D009646:Norleucine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D010434:Pepsin A / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D012083:Renin / Q000097:blood; D012453:Saimiri; D013154:Spleen / Q000201:enzymology; D013552:Swine; D000092502:Renin Inhibitors
D000614:Aminocaproates; D002402:Cathepsin D; D005665:Furosemide; D009025:Morpholines; D009646:Norleucine; D010434:Pepsin A; D012083:Renin; D000092502:Renin Inhibitors; C059042:BW 175