N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA): A potential cognitive enhancer with MAO inhibitor properties.

Giuseppe Di Giovanni, Isela García, Roberto Colangeli, Massimo Pierucci, Marcos L. Rivadulla, Elena Soriano, Mourad Chioua, Laura Della Corte, Matilde Yáñez, Philippe De Deurwaerdère, Yagamare Fall, José Marco-Contelles
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

© 2014 John Wiley & Sons Ltd.


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