Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity
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 mitochondri...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996105001397 |
| _version_ | 1824026240900661248 |
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| author | Carine Cleren Anatoly A. Starkov Noel Y. Calingasan Beverly J. Lorenzo Junya Chen M. Flint Beal |
| author_facet | Carine Cleren Anatoly A. Starkov Noel Y. Calingasan Beverly J. Lorenzo Junya Chen M. Flint Beal |
| author_sort | Carine Cleren |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T11:11:51Z |
| format | Article |
| id | doaj.art-569e78ed730e42e9a81a69f5bcf78932 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T11:11:51Z |
| publishDate | 2005-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-569e78ed730e42e9a81a69f5bcf789322022-12-21T20:24:11ZengElsevierNeurobiology of Disease1095-953X2005-12-01203701708Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicityCarine Cleren0Anatoly A. Starkov1Noel Y. Calingasan2Beverly J. Lorenzo3Junya Chen4M. Flint Beal5Corresponding author. Fax: +1 212 746 8276.; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USAPromethazine (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.http://www.sciencedirect.com/science/article/pii/S0969996105001397PromethazineMPTPMPP+ParkinsonNeuroprotectionMitochondria |
| spellingShingle | Carine Cleren Anatoly A. Starkov Noel Y. Calingasan Beverly J. Lorenzo Junya Chen M. Flint Beal Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity Neurobiology of Disease Promethazine MPTP MPP+ Parkinson Neuroprotection Mitochondria |
| title | Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity |
| title_full | Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity |
| title_fullStr | Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity |
| title_full_unstemmed | Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity |
| title_short | Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity |
| title_sort | promethazine protects against 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine neurotoxicity |
| topic | Promethazine MPTP MPP+ Parkinson Neuroprotection Mitochondria |
| url | http://www.sciencedirect.com/science/article/pii/S0969996105001397 |
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