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Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity
- Source :
- Neurobiology of Disease, Vol 20, Iss 3, Pp 701-708 (2005)
- Publication Year :
- 2005
- Publisher :
- Elsevier, 2005.
-
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.
Details
- Language :
- English
- ISSN :
- 1095953X
- Volume :
- 20
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- Neurobiology of Disease
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.569e78ed730e42e9a81a69f5bcf78932
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.nbd.2005.05.022