The Neuropathology of Movement Disorders in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) and Methcathinone (Ephedrone) Addictions

An irreversible parkinsonian-like movement disorder has been described in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methcathinone (ephedrone) abusers. MPTP damages mitochondrial respiration, stimulates formation of reactive oxygen species, and contributes to apoptotic cell death in dopaminergic neurons within the substantia nigra pars compacta. Parkinsonism caused by MPTP toxicity clinically is indistinguishable from idiopathic Parkinson's disease (PD). This feature successfully has been used to produce experimental models of PD. Methcathinone may be synthesized in a home environment from ephedrine-containing cold remedies in the presence of potassium permanganate and vinegar. This manner of synthesis exposes users to an extremely high manganese load that damages pallidar neurons and glial cells and clinically presents as manganism-a distinctive movement disorder with disabling postural instability, gait and speech disturbance, foot dystonia, akinesia, and micrographia. Due to easily available components and simple synthesis, methcathinone still presents a continuing public health hazard in many Eastern European countries. Usage of drugs that have been synthesized in uncontrolled environments puts abusers at a high risk for developing undesired and unexpected complications, including irreversible movement disturbances related to the toxic effects of contaminants coincidentally produced during synthesis.