Opposite vascular activity of (R)-apomorphine and its oxidised derivatives. Endothelium-dependent vasoconstriction induced by the auto-oxidation metabolite
| Autor: | Eugenia García-Zaragozá, Rafael Ballesteros, Juan Moragues, Pilar D'Ocon, Belén Abarca, Patricia Bielsa, M. Antonia Noguera |
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| Rok vydání: | 2003 |
| Předmět: |
Apomorphine
Calcium Channels L-Type Endothelium Metabolite Radioligand Assay chemistry.chemical_compound Drug Discovery medicine Animals Vasoconstrictor Agents Enzyme Inhibitors Rats Wistar Aorta Cerebral Cortex Pharmacology Dose-Response Relationship Drug biology Organic Chemistry Quinones Stereoisomerism General Medicine Receptors Adrenergic alpha Receptors GABA-A Acetylcholine In vitro Rats Nitric oxide synthase medicine.anatomical_structure Biochemistry chemistry Vasoconstriction Biophysics biology.protein Female Endothelium Vascular Nitric Oxide Synthase medicine.symptom Oxidation-Reduction Blood vessel medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 38:501-511 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/s0223-5234(03)00057-6 |
| Popis: | We have synthetised a series of oxidised apomorphine derivatives (orto and para quinones 2-5), in order to analyse their vascular activity. We have performed radioligand binding assays on rat cortical membranes and functional studies on rat aortic rings. Instead the relaxant activity exhibited by (R)-apomorphine, o-quinones 2, 4, show contractile activity dependent on endothelium in rat aortic rings. Compound 2, the main metabolite of (R)-apomorphine auto-oxidation, was the product which showed enhanced contractile activity by a complex mechanism related to activation of Ca(2+) channels through release and/or inhibition of endothelial factors. Moreover, this compound disrupts the endothelial function as shows the lack of response to acetylcholine observed in vessels pretreated with it. |
| Databáze: | OpenAIRE |
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