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) |
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Pages (from-to) | 1224-1237 |
Number of pages | 14 |
Journal | Neurochemical Research |
Volume | 32 |
Issue number | 7 |
DOIs | |
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