Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity Academic Article uri icon


MeSH Major

  • Dopamine
  • Neurons
  • Parkinsonian Disorders
  • Promethazine
  • Substantia Nigra


  • 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.

publication date

  • December 2005



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2005.05.022

PubMed ID

  • 16126396

Additional Document Info

start page

  • 701

end page

  • 8


  • 20


  • 3