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MHP-133, a Drug with Multiple CNS Targets: Potential for Neuroprotection and Enhanced Cognition

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An Erratum to this article was published on 01 September 2007

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.

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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.

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Author notes

  1. Maria A. Hernandez

    Present address: College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, 33328, USA

Authors and Affiliations

  1. Alzheimer’s Research Center, Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA, 30912, USA

    Jerry J. Buccafusco, Alvin V. Terry (Jr) & Ramamohana R. Jonnala

  2. Medical Research Service, Veterans Administration Medical Center, Augusta, GA, 30904, USA

    Jerry J. Buccafusco

  3. School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA

    James C. Powers & Maria A. Hernandez

  4. Department of Psychology, University of Kentucky, Lexington, KY, 40546, USA

    Mark A. Prendergast

Authors
  1. Jerry J. Buccafusco
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  2. James C. Powers
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  3. Maria A. Hernandez
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  4. Mark A. Prendergast
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Corresponding author

Correspondence to Jerry J. Buccafusco.

Additional information

Special issue dedicated to Dr. Moussa Youdim.

An erratum to this article can be found at http://dx.doi.org/10.1007/s11064-007-9489-4

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Buccafusco, J.J., Powers, J.C., Hernandez, M.A. et al. MHP-133, a Drug with Multiple CNS Targets: Potential for Neuroprotection and Enhanced Cognition. Neurochem Res 32, 1224–1237 (2007). https://doi.org/10.1007/s11064-007-9294-0

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  • DOI: https://doi.org/10.1007/s11064-007-9294-0

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