N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA): A potential cognitive enhancer with MAO inhibitor properties.
CNS Neurosci Ther. 2014-05-21; 20(7): 633-640
DOI: 10.1111/cns.12284
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BACKGROUND: A considerable body of human and animal experimental evidence links
monoaminergic systems and cognition. Monoamine oxidase inhibitors (MAOIs), being
able to enhance monoaminergic transmission and having neuroprotective properties,
might represent a promising therapeutic strategy in cognitive impairment in
Alzheimer’s disease (AD) and other dementias.
METHODS: The MAO-A and MAO-B inhibition profile of
N-(furan-2-ylmethyl)-N-prop-2-yn-1-amine derivates (compounds 1-3) were evaluated
by fluorimetric method and their absorption, distribution, metabolism, excretion,
and toxicity (ADMET) properties estimated. The effects of the selected compound
1, N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA), were evaluated on the
basic synaptic transmission, long-term potentiation (LTP), and excitability in
the dentate gyrus (DG) of the hippocampus of anesthetized rats.
RESULTS: F2MPA is a partially reversible inhibitor of hMAO-B, with moderate to
good ADMET properties and drug-likeness. Intraperitoneal administration of 1
mg/kg F2MPA greatly enhanced basic synaptic transmission, induced LTP, and
potentiated electrically induced LTP in the dentate gyrus. Moreover, F2MPA did
not modify seizure threshold of pilocarpine-induced convulsion in CD1 mice.
CONCLUSION: Our findings suggest that, the MAO-B inhibitor, F2MPA improves DG
synaptic transmission without triggering pathological hyperexcitability.
Therefore, F2MPA shows promise as a potential cognition-enhancing therapeutic
drug.
© 2014 John Wiley & Sons Ltd.