Dopaminergic pharmacology and antioxidant properties of pukateine, a natural product lead for the design of agents increasing dopamine neurotransmission

Dajas-Bailador F.A.; bonilla, c; Dajas, F; Asencio M.; Cassels, B.K.; Scorza, M.C.; Echeverry, C; Reyes-Parada, M; Silveira, R.; Protais, P; Russell G.

Keywords: phenyl, model, acid, performance, system, rat, antioxidants, animals, transmission, hydrogen, binding, assay, brain, rats, dopamine, disease, stress, peroxidation, mitochondrion, microdialysis, site, antioxidant, experiment, male, receptor, agents, oxidase, methyl, apomorphine, level, agent, tissue, maleate, drug, inhibitors, article, lipid, aporphines, activity, neurotransmission, amine, controlled, animal, oxidative, study, 7, 8, 1, 3, substance, aporphine, derivative, parkinson, priority, nonhuman, journal, Rats,, Sprague-Dawley, 2, 1h, Radioligand, Nervous, Reactive, 5, Stimulating, central, psychomotor, dopaminergic, Synaptic, thiobarbituric, tetrahydro, (flavin, containing), Monoamine, oxidopamine, ol, chloro, 2,3,4,5, benzazepin, raclopride

Abstract

The dopaminergic and antioxidant properties of pukateine [(R)-11-hydroxy-1,2-methylenedioxyaporphine, PUK], a natural aporphine derivative, were analyzed in the rat central nervous system. At dopamine (DA) D1 ([3H]-SCH 23390) and D2 ([3H]-raclopride) binding sites, PUK showed IC50 values in the submicromolar range (0.4 and 0.6 ?M, respectively). When the uptake of tritiated dopamine was assayed by using a synaptosomal preparation, PUK showed an IC50 = 46 ?M. In 6-hydroxydopamine unilaterally denervated rats, PUK (8 mg/kg but not 4 mg/kg) elicited a significant contralateral circling, a behavior classically associated with a dopaminergic agonist action. When perfused through a microdialysis probe inserted into the striatum, PUK (340 ?M) induced a significant increase in dopamine levels. In vitro experiments with a crude rat brain mitochondrial suspension showed that PUK did not affect monoamine oxidase activities, at concentrations as high as 100 ?M. PUK potently IC50 = 15 ?M and dose-dependently inhibited the basal lipid peroxidation of a rat brain membrane preparation. As a whole, PUK showed a unique profile of action, comprising an increase in extracellular DA, an agonist-like interaction with DA receptors, and antioxidant activity. Thus, PUK may be taken as a lead compound for the development of novel therapeutic strategies for Parkinson disease. Copyright (C) 1999 Elsevier Science Inc.

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Título de la Revista: General Pharmacology: The Vascular System
Volumen: 32
Número: 3
Editorial: Society of Laparoendoscopic Surgeons
Fecha de publicación: 1999
Página de inicio: 373
Página final: 379
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0033046305&partnerID=q2rCbXpz