DOPAMINE, 6-HYDROXYDOPAMINE, IRON, AND DIOXYGEN - THEIR MUTUAL INTERACTIONS AND POSSIBLE IMPLICATION IN THE DEVELOPMENT OF PARKINSONS-DISEASE

The reactions of dopamine (1-amino-2-(3,4-dihydroxyphenyl)-ethane DA), 5-hydroxydopamine (5-OHDA), and 6-hydroxydopamine (6-OHDA), with mole cular oxygen - with and without the addition of catalytic amounts of i ron(III) and other metal ions - have been studied and the implication of these results with respect to the chemistry involved in the progres s of Parkinson's disease is discussed, In the presence of O-2 DA react s spontaneously without the necessity of metal-ion catalysis under the production of stoichiometric amounts of H2O2, to form initially pink dopaminochrome, which is not stable and reacts further (without the co nsumption of dioxygen) to form the insoluble polymeric material known as 'melanine'. DA reacts with iron(III) yielding an intermediate 1:1 c omplex, which decomposes releasing Fe(II) and the semiquinone, which r eacts further under involvement of both Fr(III) and dioxygen. 6-OHDA r eacts without showing the necessity of such an intermediate, and it is shown to be able to release iron as Fe(II) from ferritine. On the oth er hand, it is shown (in vitro) that Fe(II) reacts in a Fenton type re action with DA and the present H2O2 producing 5-OHDA and especially 6- OHDA. Based on these mutual interacting reactions a mechanism for the initiation and progress of Parkinson's disease is suggested. The catal ytic effects of some other transition-metal ions are presented and an explanation for the peculiarly toxic effects of manganese(II) is put f orward. Finally, a possible reason for the effect that nicotine has in the mitigation of Parkinson's disease is discussed.