2018, Volume 21, Issue 2
Virtual screening of trabenazine and Its deuterated analogue against the synaptic vesicular amine transporter
1 National Research and Development Institute for Cryogenics and Isotopic Technologies - ICSI Rm. Valcea, Uzinei Street no. 4, PO Box Râureni 7, 240050, Râmnicu Vâlcea, Romania
2 Biotech Corp SRL, Râmnicu Vâlcea, Romania
3 University of Bucharest, Faculty of Physics, 3Nano-SAE Research Centre, Bucharest-Măgurele, Romania
Tetrabenazine (TBZ) and its isotopic isomer, deutetrabenazine (DEU), are both approved, investigational drugs. TBZ is an older drug presently used primarily, for the symptomatic treatment of various hyperkinetic disorders. Its analogue, DEU, is the first deuterated drug recently approved by the US Food and Drug Administration for the treatment of related movement disorders associated with Huntington’s disease. Both TBZ and DEU act as inhibitors of the synaptic vesicular monoamine transporter (VMAT2). The aim of this paper was to use molecular docking, a cheminformatics tool, to virtually screen TBZ and DEU against a homologue model of VMAT2, in order to predict the binding conformations and the binding affinity. Docking results indicates that DEU is a stronger binder than TBZ. However, further studies, including X-ray crystallography, are necessary to elucidate the complete mechanisms of action of TBZ and its deuterated analogue.
trabenazine, deutetrabenazine, isotopic isomer, deuterium, docking, VMAT2
Tag search trabenazine deutetrabenazine isotopic isomer deuterium docking VMAT2