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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
1993-8-19
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| pubmed:abstractText |
The angiotensin II (AII) antagonistic action of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-1H-benzi mid azole-7 - carboxylic acid (CV-11974) was examined in in vitro assay systems, including AII receptor binding assay using membrane fractions of bovine adrenal cortex or rabbit aorta and AII-induced contraction assay using rabbit aortic strips, and CV-11974 and its prodrug, (+/-)1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylate (TCV-116), were examined in an in vivo system of AII-induced pressor response in conscious rats. DuP 753 or EXP3174 (the main active metabolite of DuP 753) was used as the reference compound. CV-11974 inhibited the binding of [125I] AII to the bovine adrenal cortical membrane and rabbit aortic membrane with IC50 values of 1.12 x 10(-7) and 2.86 x 10(-8) M, respectively. Similar results were obtained with EXP3174. CV-11974 interacted with AII in these membrane fractions with subtype 1 receptor in a competitive manner. CV-11974 at 10(-5) M did not affect the binding of [125I]AII to subtype 2 (AT2) receptor in bovine cerebellum. CV-11974 selectively inhibited the AII-induced contraction of rabbit aortic strips in a noncompetitive manner (pD' 2, 9.97); it had no effects on the contraction induced by norepinephrine, KCl, serotonin, prostaglandin F2 alpha or endothelin. EXP3174 showed a pD'2 value of 8.95 for the AII-induced contraction. CV-11974 given intravenously and TCV-116 given orally inhibited the AII-induced pressor response in rats with ID50 values of 0.033 mg/kg and 0.069 mg/kg, respectively. These effects of CV-11974 and TCV-116 were 12 and 48 times more potent than those of EXP3174 and DuP 753, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin III,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin Receptor Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Antihypertensive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzimidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Biphenyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/EXP3174,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Losartan,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/candesartan,
http://linkedlifedata.com/resource/pubmed/chemical/candesartan cilexetil
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0022-3565
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
266
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
114-20
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:8331552-Adrenal Cortex,
pubmed-meshheading:8331552-Angiotensin II,
pubmed-meshheading:8331552-Angiotensin III,
pubmed-meshheading:8331552-Angiotensin Receptor Antagonists,
pubmed-meshheading:8331552-Animals,
pubmed-meshheading:8331552-Antihypertensive Agents,
pubmed-meshheading:8331552-Aorta,
pubmed-meshheading:8331552-Benzimidazoles,
pubmed-meshheading:8331552-Biphenyl Compounds,
pubmed-meshheading:8331552-Blood Pressure,
pubmed-meshheading:8331552-Cattle,
pubmed-meshheading:8331552-Imidazoles,
pubmed-meshheading:8331552-Iodine Radioisotopes,
pubmed-meshheading:8331552-Kinetics,
pubmed-meshheading:8331552-Losartan,
pubmed-meshheading:8331552-Male,
pubmed-meshheading:8331552-Muscle, Smooth, Vascular,
pubmed-meshheading:8331552-Muscle Contraction,
pubmed-meshheading:8331552-Prodrugs,
pubmed-meshheading:8331552-Protein Binding,
pubmed-meshheading:8331552-Rabbits,
pubmed-meshheading:8331552-Rats,
pubmed-meshheading:8331552-Rats, Sprague-Dawley,
pubmed-meshheading:8331552-Substrate Specificity,
pubmed-meshheading:8331552-Tetrazoles
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| pubmed:year |
1993
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| pubmed:articleTitle |
Pharmacological profile of a highly potent and long-acting angiotensin II receptor antagonist, 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl]-1H-benzimidazole-7-carboxylic acid (CV-11974), and its prodrug, (+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5- yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate (TCV-116).
|
| pubmed:affiliation |
Pharmaceutical Research Laboratories I, Takeda Chemical Industries, Ltd., Osaka, Japan.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro
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