Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction.
Ergoline-derived dopamine receptor agonists, like pergolide or bromocryptine, have recently attracted attention as potential neuroprotective drugs. The classical mixed type dopamine D1 and D2 receptor agonist apomorphine, although used clinically in the therapy of Parkinson's disease, has never been examined for any properties related to neuroprotection. In this paper, we examine the effects of 0.1-100 microM apomorphine on ascorbate/iron-stimulated free radical processes in rat brain mitchondrial fraction. Lipid peroxidation as assayed by the thiobarbituric acid reaction can be completely inhibited by submicromolar concentrations of apomorphine (0.3 microM with 2.5 microM Fe2+ and 0.6 microM with 5.0 microM Fe2+), which proved to be more than twice as effective as desferrioxamine and twenty times as compared with dopamine. The inhibition of lipid peroxidation in mitochondria correlates with an increased rate of apomorphine oxidation. The formation of protein carbonyls, which is generally less sensitive to antioxidants, could be significantly reduced by apomorphine. In the model system we employed, apomorphine was more active than dopamine, desferrioxamine, or pergolide in preventing the formation of thiobarbituric reactive substances. The time course of the reaction suggests that apomorphine acts as a radical scavenger and that its iron chelating properties may not be of major importance. Since oxidative stress has been implicated in Parkinson's disease, the role of apomorphine as a neuroprotective is worthy of examination.
Gassen
M
M
Department of Pharmacology, Bruce Rappaport Family Research Institute, Faculty of Medicine, Technion, Haifa, Israel.
Glinka
Y
Y
Pinchasi
B
B
Youdim
M B
MB
D000818:Animals; D001058:Apomorphine / Q000737:chemistry*; D001923:Brain Chemistry; D003676:Deferoxamine / Q000737:chemistry; D004298:Dopamine / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry*; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016166:Free Radical Scavengers; D003676:Deferoxamine; D001058:Apomorphine; D004298:Dopamine