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

doi:10.1007/s11064-007-9294-0

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

Pharmacology and Toxicology

Research output: Contribution to journal › Article › peer-review

7 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 language	English (US)
Pages (from-to)	1224-1237
Number of pages	14
Journal	Neurochemical Research
Volume	32
Issue number	7
DOIs	https://doi.org/10.1007/s11064-007-9294-0
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s11064-007-9294-0

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

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.",

keywords = "5HT receptors, Cholinergic receptors, Cognition, Delayed matching-to-sample, Drug development, Neurodegeneration, Non-human primates",

author = "Buccafusco, {Jerry J.} and Powers, {James C.} and Hernandez, {Maria A.} and Prendergast, {Mark A.} and Terry, {Alvin V.} and Jonnala, {Ramamohana R.}",

note = "Funding Information: Acknowledgments This work was supported by a grant from the Callaway Foundation of Georgia, by the Medical College of Georgia Alzheimer{\textquoteright}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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AU - Jonnala, Ramamohana R.

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N2 - 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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MHP-133, a drug with multiple CNS targets: Potential for neuroprotection and enhanced cognition

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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