Promethazine protects against 3-nitropropionic acid-induced neurotoxicity.

Abstract

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.

• Authors: Carine Cleren, Noel Y Calingasan, Anatoly Starkov, Carine Jacquard, Junya Chen, Emmanuel Brouillet, M Flint Beal
• Journal: Neurochemistry international (Neurochem Int) Vol. 56 Issue 2 Pg. 208-12 (Jan 2010) ISSN: 1872-9754 [Electronic] England
• PMID: 19852992 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Neuroprotective Agents
• Nitro Compounds
• Propionates
• Succinate Dehydrogenase
• Promethazine
• 3-nitropropionic acid

Topics

• Amyotrophic Lateral Sclerosis (chemically induced, prevention & control)
• Animals
• Brain Ischemia (chemically induced, prevention & control)
• Disease Models, Animal
• Huntington Disease (chemically induced, prevention & control)
• Male
• Mice
• Neuroprotective Agents (pharmacology)
• Nitro Compounds (toxicity)
• Promethazine (pharmacology)
• Propionates (toxicity)
• Rats
• Rats, Inbred Lew
• Succinate Dehydrogenase (metabolism)