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Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity
| Content Provider | Directory of Open Access Journals (DOAJ) |
|---|---|
| Author | Anatoly A. Starkov Noel Y. Calingasan M. Flint Beal Carine Cleren Junya Chen Beverly J. Lorenzo |
| Abstract | Promethazine (PMZ) is an FDA-approved antihistaminergic drug that was identified as a potentially neuroprotective compound in the NINDS screening program. PMZ accumulates in brain mitochondria in vivo and inhibits Ca2+-induced mitochondrial permeability transition pore (PTP) in rat liver mitochondria in vitro. We hypothesized that PMZ may have a protective effect in a mitochondrial toxin model of Parkinson's disease (PD). Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) sustained a significant loss of dopaminergic neurons within the SNpc that was strongly attenuated by PMZ treatment. However, neither striatal MPP+ concentrations nor MPTP-induced inhibition of mitochondrial complex I were affected by PMZ treatment. In isolated mouse brain mitochondria, PMZ partially prevented and reversed MPP+-induced depolarization of membrane potential and inhibited the Ca2+-induced PTP in brain mitochondria. The sum of data indicates that PMZ is a strong neuroprotective agent capable of protecting dopaminergic neurons against MPTP toxicity in vivo. |
| Related Links | http://www.sciencedirect.com/science/article/pii/S0969996105001397 |
| e-ISSN | 1095953X |
| DOI | 10.1016/j.nbd.2005.05.022 |
| Journal | Neurobiology of Disease |
| Issue Number | 3 |
| Volume Number | 20 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2005-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Neurosciences. Biological Psychiatry. Neuropsychiatry Promethazine Mptp Mpp+ Parkinson Neuroprotection Mitochondria |
| Content Type | Text |
| Resource Type | Article |
