Methamphetamine oxidative stress

Cubells, J.F., Rayport, S., Raygendran, G., Sulzer, D. Methamphetamine neurotoxicity involves vac-uolation of endocytic organelles and dopamine-dependent intracellular oxidative stress. J. Neurosci. 14 2260, 1994. 

A final pharmacological strategy for treatment of Parkinson s disease comes from enzyme inhibition. This was initally done with an MAO inhibitor, L-deprenyl (selegiline, Eldepryl), but more recent drugs have become available that are COMT inhibitors. L-Deprenyl is an inhibitor of MAOB, which is the form of MAO selective to dopamine. Thus, it may increase the amount of available dopamine for release. Second, it may protect dopamine neurons by reducing the oxidative stress concomitant with dopamine metabolism (Olanow 1997). Third, L-deprenyl is metabolized into amphetamine and methamphetamine, which may contribute to their antiparkinsonian effects. Unlike other treatments for Parkinson s disease, L-deprenyl seems to slow the progression of the disease. Tolcapone (Tasmar) is a COMT inhibitor, which prevents extracellular breakdown of dopamine. 

When the methamphetamine analog MDMA is administered, selective and persistent neurochemical deficits are observed in the serotonergic terminal regions. DA is essential for these neurochemical deficits. Reducing conditions reverse these amphetamine-induced changes, providing evidence that oxidative stress is an important component in causing the neurochemical deficits. 

---