Comparative Analysis of the Neurochemical Profile and MAO Inhibition Properties of N-(Furan-2-ylmethyl)-N-methylprop-2-yn-1-amine

Philippe De Deurwaerdère, Claudia Binda, Rémi Corne, Cosima Leone, Aurora Valeri, Massimo Valoti, Rona R. Ramsay, Yagamare Fall, José Marco-Contelles
ACS Chem. Neurosci.. 2016-12-30; 8(5): 1026-1035
DOI: 10.1021/acschemneuro.6b00377

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De Deurwaerdère P(1), Binda C(2), Corne R(1), Leone C(3), Valeri A(4), Valoti M(3), Ramsay RR(5), Fall Y(6), Marco-Contelles J(7).

Author information:
(1)Centre National de la Recherche Scientifique , Institut des Maladies Neurodégénératives, UMR CNRS 5293, 33000 Bordeaux, France.
(2)Dipartimento di Biologia e Biotecnologie, Università di Pavia , 27100 Pavia, Italy.
(3)Dipartimento di Scienze della Vita, Università di Siena , 53100 Siena, Italy.
(4)Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia , 06123 Perugia, Italy.
(5)Biomedical Sciences Research Complex, University of St Andrews , St Andrews KY16 9ST, U.K.
(6)Departamento de Química Orgánica, Universidad de Vigo , 36310 Vigo, Spain.
(7)Laboratory of Medicinal Chemistry, IQOG, CSIC , 28006 Madrid, Spain.

The regulation of brain monoamine levels is paramount for cognitive functions, and the monoamine oxidase (MAO A and B) enzymes play a central role in these processes. The aim of this study was to evaluate whether the procognitive
properties exerted by propargylamine N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA) are related to changes in monoamine content via MAO inhibition. In vivo microdialysis and ex vivo amine metabolite measurement demonstrated region-specific alterations in monoamine metabolism that differ from both of the classic MAO A and MAO B inhibitors, clorgyline and l-deprenyl, respectively. Although all the inhibitors (1 and 4 mg/kg) increased cortical serotonin tissue content, only F2MPA increased the levels of cortical noradrenaline. In the striatum, clorgyline (1 mg/kg), but not
F2MPA (1 mg/kg), reduced extracellular levels of dopamine metabolites at rest or stimulated by the intrastriatal application of the MAO substrate 3-methoxytyramine. In vitro, F2MPA exhibited a low affinity toward MAO B and MAO
A. Nonetheless, it modified the B form of MAO, forming a flavin adduct structurally similar to that with deprenyl. F2MPA was rapidly metabolized in the presence of rat but not human microsomes, producing a hydroxylated derivative. In conclusion, the effect of F2MPA on cognition may arise from monoaminergic changes in the cortex, but the role of MAO in this process is likely to be negligible, consistent with the poor affinity of F2MPA for MAO.


Auteurs Bordeaux Neurocampus