Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity

Carine Cleren; Anatoly A. Starkov; Noel Y. Calingasan; Beverly J. Lorenzo; Junya Chen; M. Flint Beal

Neurobiology of Disease (Dec 2005)

Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity

Carine Cleren,
Anatoly A. Starkov,
Noel Y. Calingasan,
Beverly J. Lorenzo,
Junya Chen,
M. Flint Beal

Affiliations

Carine Cleren: Corresponding 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, USA
Anatoly A. Starkov: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USA
Noel Y. Calingasan: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USA
Beverly J. Lorenzo: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USA
Junya Chen: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USA
M. Flint Beal: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A-501, New York, NY 10021, USA

Journal volume & issue: Vol. 20, no. 3
pp. 701 – 708

Abstract

Read online

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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal

Abstract

Keywords