The high‐affinity D2/D3 agonist D512 protectsPC12 cells from 6‐OHDA‐induced apoptotic cell death and rescues dopaminergic neurons in theMPTPmouse model of Parkinson's disease

In this study, in vitro and in vivo experiments were carried out with the high‐affinity multifunctional D2/D3 agonist D‐512 to explore its potential neuroprotective effects in models of Parkinson's disease and the potential mechanism(s) underlying such properties. Pre‐treatment with D‐512 in vitro was found to rescue rat adrenal Pheochromocytoma PC 12 cells from toxicity induced by 6‐hydroxydopamine administration in a dose‐dependent manner. Neuroprotection was found to coincide with reductions in intracellular reactive oxygen species, lipid peroxidation, and DNA damage. In vivo , pre‐treatment with 0.5 mg/kg D‐512 was protective against neurodegenerative phenotypes associated with systemic administration of MPTP , including losses in striatal dopamine, reductions in numbers of DA ergic neurons in the substantia nigra ( SN ), and locomotor dysfunction. These observations strongly suggest that the multifunctional drug D‐512 may constitute a novel viable therapy for Parkinson's disease. image Neuroprotective properties of dopamine D2/D3 agonist D‐512 was evaluated both in vitro and in vivo models of Parkinson's disease (PD). D‐512 rescued PC12 cells from toxicity induced by 6‐hydroxydopamine (6‐OHDA). D‐512 reduced intracellular reactive oxygen species and lipid peroxidation as well as protection of DNA damage from toxicity of 6‐OHDA. D‐512 was protective against neurodegenerative phenotypes induced by MPTP in mouse. Our studies strongly suggest that D‐512 with its multifunctional property may constitute a novel viable therapy for Parkinson's disease.