FIGURE 4

Possible mechanism for the neurotoxicity produced by methamphetamine. This amine enters dopamine neurones/terminals via the dopamine transporter (DAT) and then releases dopamine from vesicles and prevents storage there by blocking the vesicular transporter (VMAT2). Methamphetamine also inhibits the activity of mitochondrial MAO involved in the catabolism of dopamine while increasing its synthesis by stimulating tyrosine hydroxylase. The net result is an increase in cytostolic dopamine, which may be metabolised to reactive dopamine metabolites, resulting in neuronal damage and degeneration. Adapted from Larsen et al. (2002).