Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of alpha sub(3) beta sub(4) nicotinic acetylcholine receptor
9 N-alkylated derivatives of dextromethorphan are synthesized and studied as non-competitive inhibitors of alpha 3 beta 4 nicotinic acetylcholine receptors (nAChRs). In vitro activity towards alpha 3 beta 4 nicotinic acetylcholine receptor is determined using a patch-clamp technique and is in the mi...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2014-02, Vol.22 (24), p.6846-6856 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | Jozwiak, Krzysztof Targowska-Duda, Katarzyna M Kaczor, Agnieszka A Kozak, Joanna Ligeza, Agnieszka Szacon, Elzbieta Wrobel, Tomasz M Budzynska, Barbara Biala, Grazyna nal, Emilia Poso, Antti Wainer, Irving W Matosiuk, Dariusz |
| description | 9 N-alkylated derivatives of dextromethorphan are synthesized and studied as non-competitive inhibitors of alpha 3 beta 4 nicotinic acetylcholine receptors (nAChRs). In vitro activity towards alpha 3 beta 4 nicotinic acetylcholine receptor is determined using a patch-clamp technique and is in the micromolar range. Homology modeling, molecular docking and molecular dynamics of ligand-receptor complexes in POPC membrane are used to find the mode of interactions of N-alkylated dextromethorphan derivatives with alpha 3 beta 4 nAChR. The compounds, similarly as dextromethorphan, interact with the middle portion of alpha 3 beta 4 nAChR ion channel. Finally, behavioral tests confirmed potential application of the studied compounds for the treatment of addiction. |
| doi_str_mv | 10.1016/j.bmc.2014.10.036 |
| format | Article |
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| source | Elsevier ScienceDirect Journals Complete |
| title | Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of alpha sub(3) beta sub(4) nicotinic acetylcholine receptor |
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