Molecular pharmacology of LR-B/081, a new non-peptide angiotensin AT1 receptor antagonist
| Autor: | Marco Criscuoli, Aldo Salimbeni, Alessandro Subissi, Anna Rita Renzetti |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
Stereochemistry Angiotensin II receptor antagonist Pyrimidinones Thiophenes Binding Competitive Angiotensin Receptor Antagonists Cerebellum Renin–angiotensin system medicine Animals Humans Receptor Pharmacology Angiotensin II receptor type 1 Molecular Structure Chemistry Angiotensin II Rats Losartan Mechanism of action Cerebellar cortex Adrenal Cortex Cattle medicine.symptom medicine.drug |
| Zdroj: | European Journal of Pharmacology: Molecular Pharmacology. 290:151-156 |
| ISSN: | 0922-4106 |
| DOI: | 10.1016/0922-4106(95)90028-4 |
| Popis: | This report describes the molecular pharmacological properties of LR-B/081 (methyl 2-[[4-butyl-2-methyl-6-oxo-5-[ [2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-yl]methyl]-1 (6H)-pyrimidinyl]methyl]-3-thiophenecarboxilate), a novel non-peptide angiotensin II receptor antagonist. This compound potently displaced [ 3 H]angiotensin II from angiotensin AT 1 ( K i = 1.4 nM, rat adrenal cortex), but not from angiotensin AT 2 ( K i > 1 ω M, bovine cerebellar cortex) receptors and did not show affinity for other receptor systems ( K i > 10 ω M). In saturation studies, LR-B/081 both increased K D and decreased B max values in a dose-dependent fashion. The rate of dissociation of [ 3 H]angiotenin II from angiotensin AT 1 receptors was not affected by the presence of 1 ωM LR-B/081 and the association rate of [ 3 H]angiotensin II was not decreased by the presence of 1 or 30 nM LR-B/081, indicating that the B max reduction was not due to an allosteric interaction or to a delay in reaching the steady-state conditions. These data underline the complexity of the antagonistic nature of LR-B/081, presenting features of both competitive and noncompetitive antagonism. |
| Databáze: | OpenAIRE |
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