6533b85bfe1ef96bd12ba0fe
RESEARCH PRODUCT
Opposite vascular activity of (R)-apomorphine and its oxidised derivatives. Endothelium-dependent vasoconstriction induced by the auto-oxidation metabolite
Eugenia García-zaragozáRafael BallesterosJuan MoraguesPilar D'oconBelén AbarcaPatricia BielsaM. Antonia Noguerasubject
ApomorphineCalcium Channels L-TypeEndotheliumMetaboliteRadioligand Assaychemistry.chemical_compoundDrug DiscoverymedicineAnimalsVasoconstrictor AgentsEnzyme InhibitorsRats WistarAortaCerebral CortexPharmacologyDose-Response Relationship DrugbiologyOrganic ChemistryQuinonesStereoisomerismGeneral MedicineReceptors Adrenergic alphaReceptors GABA-AAcetylcholineIn vitroRatsApomorphineNitric oxide synthasemedicine.anatomical_structureBiochemistrychemistryVasoconstrictionBiophysicsbiology.proteinFemaleEndothelium VascularNitric Oxide Synthasemedicine.symptomOxidation-ReductionVasoconstrictionAcetylcholineBlood vesselmedicine.drugdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-05-01 | European Journal of Medicinal Chemistry |