Promethazine protects against 3-nitropropionic acid-induced neurotoxicity

Promethazine (PMZ), an FDA-approved antihistaminergic drug, was identified as a potentially neuroprotective compound in a NINDS screening program. It was shown to protect against ischemia in mice, to delay disease onset in a mouse model of amyotrophic lateral sclerosis and to inhibit Ca 2+-induced m...

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Bibliographic Details
Published in:Neurochemistry international 2010-01, Vol.56 (2), p.208-212
Main Authors: Cleren, Carine, Calingasan, Noel Y., Starkov, Anatoly, Jacquard, Carine, Chen, Junya, Brouillet, Emmanuel, Beal, M. Flint
Format: Article
Language:English
Subjects:
Amyotrophic Lateral Sclerosis - chemically induced
Amyotrophic Lateral Sclerosis - prevention & control
Animals
Apoptosis
Biological and medical sciences
Brain Ischemia - chemically induced
Brain Ischemia - prevention & control
Calbindin
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Fundamental and applied biological sciences. Psychology
Huntington
Huntington Disease - chemically induced
Huntington Disease - prevention & control
Male
Medical sciences
Mice
Mitochondria
Neurology
Neuroprotection
Neuroprotective Agents - pharmacology
Neurotoxicity
Nitro Compounds - toxicity
Promethazine - pharmacology
Propionates - toxicity
Rats
Rats, Inbred Lew
Succinate dehydrogenase
Succinate Dehydrogenase - metabolism
Vertebrates: nervous system and sense organs
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Summary:Promethazine (PMZ), an FDA-approved antihistaminergic drug, was identified as a potentially neuroprotective compound in a NINDS screening program. It was shown to protect against ischemia in mice, to delay disease onset in a mouse model of amyotrophic lateral sclerosis and to inhibit Ca 2+-induced mitochondrial permeability transition in rat liver mitochondria. We investigated whether PMZ could protect against the neurotoxic effects induced by 3-nitropropionic acid (3-NP), an inhibitor of the succinate dehydrogenase, used to model Huntington's disease (HD) in rats. Lewis rats receiving chronic subcutaneous infusion of 3-NP were treated with PMZ. The findings indicate that chronic PMZ treatment significantly reduced 3-NP-induced striatal lesion volume, loss of GABAergic neurons and number of apoptotic cells in the striatum. PMZ showed a strong neuroprotective effect against 3-NP toxicity in vivo.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2009.10.006