The neuroprotective efficacy of the
propargylamine TCH346 was studied in the primate model of
Parkinson's disease, the bilaterally
MPTP-treated monkey. Male rhesus monkeys received 2.5 mg
MPTP into the left carotid artery and, 8 weeks later, 1.25 mg
MPTP into the right carotid artery. Starting 2 h after the second
MPTP infusion, either 0.014 mg/kg
TCH346 or its
solvent was subcutaneously injected twice per day for 14 days. The first
MPTP treatment induced mild Parkinson symptoms, reduced right limb movements, and reduced FDOPA uptake in the left striatum. The second
MPTP treatment made Parkinson symptoms worse, reduced left limb movements, and reduced FDOPA uptake in the right striatum of
solvent-treated monkeys. In contrast, the second
MPTP treatment did not further worsen motor symptoms and did not decrease FDOPA uptake in the right striatum of TCH346-treated monkeys. Although the effects of the second
MPTP treatment were largely prevented, the effects of the first
MPTP treatment were not reversed by
TCH346. Immunohistochemical examination confirmed the dramatic loss of
dopamine cells in vehicle-treated monkeys and the preservation of these neurons in the right brain side of the TCH346-treated animals. In conclusion, systemic administration of
TCH346 prevented motor symptoms and nigrostriatal degeneration induced by
MPTP in primates.