Antidepressant-like effects of a new dihydro isoquinoline and its chemical precursors in mice: involvement of serotonin and dopaminergic systems
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Date
2021
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Publisher
NRC Research Press
Abstract
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Abstract: This study was aimed to synthesize novel 2-(2-bromophenyl)-N-phenethylacetamides and benzylisoquinoline (BIQ)
derivatives to be evaluated as antidepressant-like agents in mice. The phenethylacetamides derivatives were synthesized by
coupling aromatic amides to the backbone of 2-bromophenylacetyl chloride. The synthesis of BIQ was achieved by the reaction
between synthesized phenethylacetamides and 2-chloropyridine. The structures of compounds were established mainly by 1D
and 2D NMR spectra. Those compounds obtained with moderate to good yields were evaluated as antidepressant-like agents in
the forced swim test and the open field paradigms in mice. The possible mechanism of those active derivatives was explored by
antagonist experiments in combination with p-chloro-phenylalanine methyl ester, reserpine, sulpiride, and dopamine D1 antagonist SCH23390. Also, MAO A and B inhibition assays were performed. Docking studies between the human dopamine D3 receptor
and the higher active compound were performed. The results showed that the (2-bromophenyl)-(3,4-dihydroisoquinoline-1-yl)
methanone (4a) presented the most potent antidepressant-like effects without modifying the ambulatory activity of experimental mice. Antagonist experiments showed that 4a acted on the serotonergic and dopaminergic receptors. Docking studies
indicated a strong affinity between the human dopamine D3 receptor and 4a. Our results showed that BIQ 4a has an
antidepressant-like effect that is possibly mediated by an interaction with the presynaptic serotonin receptors and dopaminergic, D1, D2, and D3, receptors. This study highlights the pharmacological potential of halogenated BIQs in the
treatment of some depressive disorders.