MHP-133, a drug with multiple CNS targets: Potential for neuroprotection and enhanced cognition

Jerry J. Buccafusco, James C. Powers, Maria A. Hernandez, Mark A. Prendergast, Alvin V. Terry, Ramamohana R. Jonnala

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

MHP-133 is one of a novel series of compounds designed to target multiple brain substrates expected to have synergistic actions in the treatment of cognitive and neurodegenerative disorders such as Alzheimer's disease. The strategy was to develop compounds with multiple targets relevant for enhancing cognition and memory, but avoiding the serious side effects attributed to high potency cholinergic agonists. MHP-133 was shown to interact with subtypes of cholinergic, serotonergic, and imidazoline receptors and to weakly inhibit acetylcholinesterase activity. In vitro, the drug enhanced nerve growth factor (TrkA) receptor expression; it prevented excitotoxicity in a hippocampal slice preparation; and increased the secretion of soluble (non-toxic) amyloid precursor protein. MHP-133 also enhanced cognitive performance by rats and by non-human primate in tasks designed to assess working memory. The results of this study are consistent with the potential use of MHP-133 in the treatment of neurodegenerative disorders such as Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1224-1237
Number of pages14
JournalNeurochemical Research
Volume32
Issue number7
DOIs
StatePublished - Jul 2007

Keywords

  • 5HT receptors
  • Cholinergic receptors
  • Cognition
  • Delayed matching-to-sample
  • Drug development
  • Neurodegeneration
  • Non-human primates

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Buccafusco, J. J., Powers, J. C., Hernandez, M. A., Prendergast, M. A., Terry, A. V., & Jonnala, R. R. (2007). MHP-133, a drug with multiple CNS targets: Potential for neuroprotection and enhanced cognition. Neurochemical Research, 32(7), 1224-1237. https://doi.org/10.1007/s11064-007-9294-0