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


CONCLUSIONS
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.
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; School of Bioscience, Cardiff University, Cardiff, UK.
Giuseppe
G
Di Giovanni
Isela
I
García
Roberto
R
Colangeli
Massimo
M
Pierucci
Marcos L
ML
Rivadulla
Elena
E
Soriano
Mourad
M
Chioua
Laura
L
Della Corte
Matilde
M
Yáñez
Philippe
P
De Deurwaerdère
Yagamare
Y
Fall
José
J
Marco-Contelles
D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000201:enzymology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008996:Monoamine Oxidase Inhibitors; D018697:Nootropic Agents; D008995:Monoamine Oxidase
ADMET; Alzheimer's disease; Enzyme inhibition; Kinetics; Long-term potentiation; MAO-A; MAO-B; N-(furan-2-ylmethyl)-N-prop-2-yn-1-amines; Temporal lobe epilepsy