Although less commonly used, AMPT, like reserpine, serves as an effective catecholamine-depleting agent (4). By directly inhibiting tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis, the nascent synthesis of dopamine in neurons of the SNpc and ventral tegmental area (VTA) is prevented.
Both reserpine and AMPT have been used to discover new dopaminomimet-ics for the treatment of PD, but since their effects are transient (hours to days), these models are primarily useful for acute studies. In addition, neither agent can duplicate the extensive biochemical nor pathological changes seen in PD. Consequently, other models with long-lasting neurochemical and behavioral alterations have been sought using site-specific neurotoxicant injury.
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