BIOMAT Database Logo BIOMAT Database Logo

Pharmacology and pharmacokinetics of a novel nonpeptide angiotensin II receptor antagonist--DMP 811. 1995

P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Cardiovascular Diseases Research, DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0400, USA.

DMP 811 exhibited high binding affinity for the angiotensin II subtype receptor AT1 in rat adrenal tissues with an IC50 of 6 nM, but not for the subtype receptor AT2. In the isolated rabbit aorta, DMP 811 inhibited the contractile response to angiotensin II selectively and noncompetitively with a KB value of 0.1 nM. In conscious renal hypertensive rats, DMP 811 decreased blood pressure with i.v. and p.o. ED30s of 0.005 and 0.03 mg/kg, respectively (p.o. ED30 for losartan = 0.59 mg/kg). In conscious furosemide-treated dogs, DMP 811 given either at 0.3 or 1 mg/kg p.o. decreased blood pressure. DMP 811 has oral bioavailabilities of 7 and 29% in rats and dogs, respectively, after a solution dose and 8 and 13%, respectively, after a suspension or capsule dosing. Our study indicates that DMP 811 is a selective and insurmountable AT1 receptor antagonist and is a 20-fold more potent orally-active antihypertensive agent than losartan.

UI MeSH Term Description Entries
D006978 Hypertension, Renovascular Hypertension due to RENAL ARTERY OBSTRUCTION or compression. Hypertension, Goldblatt,Goldblatt Syndrome,Goldblatt Hypertension,Renovascular Hypertension,Syndrome, Goldblatt
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008297 Male Males
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001681 Biological Assay A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. Bioassay,Assay, Biological,Assays, Biological,Biologic Assay,Biologic Assays,Assay, Biologic,Assays, Biologic,Bioassays,Biological Assays

Related Publications

P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist.
October 1995, European journal of pharmacology,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Disposition of DMP 811 (L-708,404), a potent angiotensin II receptor antagonist, in the rat, monkey, and chimpanzee.
October 1995, Drug metabolism and disposition: the biological fate of chemicals,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Pharmacology of nonpeptide angiotensin II receptor antagonists.
January 1992, Annual review of pharmacology and toxicology,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Pharmacologic profiles of KRH-594, a novel nonpeptide angiotensin II-receptor antagonist.
November 1997, Journal of cardiovascular pharmacology,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Pharmacological properties of KT3-671, a novel nonpeptide angiotensin II receptor antagonist.
January 1995, Journal of cardiovascular pharmacology,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Pharmacological characterization of the novel nonpeptide angiotensin II receptor antagonist, BIBR 277.
September 1993, British journal of pharmacology,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
EXP063, a nonpeptide angiotensin II and beta adrenergic receptor antagonist.
November 1993, The Journal of pharmacology and experimental therapeutics,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Characterization of angiotensin II antagonism displayed by Ib, a novel nonpeptide angiotensin AT(1) receptor antagonist.
July 2008, European journal of pharmacology,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
Pharmacological profile of a novel nonpeptide angiotensin II subtype 1 receptor antagonist, TCV-116.
January 1994, Blood pressure. Supplement,
P C Wong, and S M Huang, and R J Ardecky, and D J Carini, and A T Chiu, and W A Price, and A M Agra, and R R Wexler, and P B Timmermans
In vivo pharmacology of L-158,809, a new highly potent and selective nonpeptide angiotensin II receptor antagonist.
July 1992, The Journal of pharmacology and experimental therapeutics,
Copied contents to your clipboard!