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We examined pharmacological profiles of KT3-671, 2-propyl-8-oxo-1-[(2'-(1H-tetrazole-5-yl) biphenyl-4-yl)methyl]- 4,5,6,7-tetrahydro-cycloheptimidazole, a newly synthesized nonpeptide angiotensin II (AII) receptor antagonist in various in vitro and in vivo studies. KT3-671 displaced specific binding of [125I]Sar1 Ile8-AII to AT1 receptor with a Ki value of 0.71 +/- 0.14 x 10(-9) M in rat liver membranes, but had no affinity for AT2 receptor in bovine cerebellar membranes (Ki > 10(-5) M). In isolated rabbit aorta, KT3-671 produced a parallel rightward shift in the concentration-response curve for AII with a pA2 value of 10.04 +/- 0.12, but had no effect on KCl-, norepinephrine (NE)-, and serotonin (5-HT)-induced contractions. In conscious normotensive rats, KT3-671 (0.3-10 mg/kg, p.o.) inhibited the AII-induced pressor response dose dependently. In renal artery-ligated hypertensive rats, KT3-671 (0.1-3 mg/kg, p.o.) decreased arterial blood pressure (BP) dose dependently. The hypotensive action of 3 mg/kg KT3-671 was maintained for at least 24 h. These results suggest that KT3-671 is a potent AT1 subtype-selective and competitive nonpeptide AII receptor antagonist and has an orally active antihypertensive effect without agonistic activity.
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
November 1995,
Japanese journal of pharmacology,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
September 1993,
British journal of pharmacology,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
January 1994,
Blood pressure. Supplement,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
September 1997,
European journal of pharmacology,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
March 2000,
Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
January 1995,
Fundamental & clinical pharmacology,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
September 1995,
European journal of pharmacology,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
September 1995,
The Journal of pharmacology and experimental therapeutics,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
October 1995,
European journal of pharmacology,
S Mochizuki, and
T Sato, and
K Furuta, and
K Hase, and
Y Ohkura, and
C Fukai, and
K Kosakai, and
S Wakabayashi, and
A Tomiyama
January 1992,
The Journal of pharmacology and experimental therapeutics,
