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 journalArticlepeer-review

7 Scopus citations


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
Pages (from-to)1224-1237
Number of pages14
JournalNeurochemical Research
Issue number7
StatePublished - Jul 2007

Bibliographical note

Funding Information:
Acknowledgments This work was supported by a grant from the Callaway Foundation of Georgia, by the Medical College of Georgia Alzheimer’s Research Center, and by salary support for JJB from the Veterans Administration Merit Review program. The authors also would like to acknowledge the fine technical assistance provided by Nancy Kille and Laura Shuster. Lastly we would like to thank Professor Moussa B. Youdim for his contributions to the field of novel drug discovery and for many enlightened conversations over the years.


  • 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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