Apomorphine Is a Potent Radical Scavenger and Protects Cultured Pheochromocytoma Cells from 6-OHDA and H2O2-Induced Cell Death

Abstract

The mixed-type dopamine D1-D2-receptor agonist apomorphine has had an impressive career as a replacement for L-dopa in the therapy for Parkinson's disease in the late stage of the disease. Earlier attempts to introduce apomorphine as a dopamine replacement had failed because of its short duration of action and gastrointestinal side effects. Presently, the pharmacokinetic problems have been overcome with sophisticated drug delivery devices, as portable infusion pumps or insulin pens. Coadministration of the peripherally acting dopamine receptor antagonist domperidone prevents the undesired noncentral effects of apomorphine, which has become the medication of choice for patients suffering from on-off fluctuations after years of L-dopa administration. The discovery that catecholamines can be cytotoxic has raised the question of the long-term effects of the treatment in Parkinson's disease with drugs like L-dopa or apomorphine on the progression of the disease. Catecholaminergic drugs can act as reducing agents and iron chelators. They can interfere with cellular redox reactions and promote the formation of free radicals, which are thought to be mediators of neurodegeneration. Damage is caused close to the site where free radicals are formed. Catecholamines can act as radical scavengers and slow down the progression of neurodegenerative diseases. In this chapter it has been demonstrated that apomorphine can act as a potent free radical scavenger in vitro and in cell culture. The balance between catecholamine toxicity and possible beneficial effects because of antioxidation was looked into in PC12 cell culture, a system to study apoptotic and necrotic cell death. Because the dopamine prodrug L-dopa and apomorphine are used in the treatment of Parkinson's disease, it is of interest to investigate the influence of these agents on the biochemical processes involved in the progression of neurodegeneration. It was found that apomorphine is a representative of a catecholamine with pronounced antioxidant effects.