Reference : Interaction of clozapine and its nitrenium ion with rat D2 dopamine receptors: in vit...
Scientific journals : Article
Engineering, computing & technology : Computer science
Human health sciences : Pharmacy, pharmacology & toxicology
Interaction of clozapine and its nitrenium ion with rat D2 dopamine receptors: in vitro binding and computational study
Dilly, Sébastien mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie >]
Liégeois, Jean-François mailto [Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique >]
Journal of Computer-Aided Molecular Design
Yes (verified by ORBi)
[en] diazepine ; nitrenium ; oxidation ; dopamine D2 receptor ; homology modelling ; molecular docking
[en] The interaction of diazepine analogues like clozapine or olanzapine with D2 receptor was greatly affected by a mixture of HRP/H2O2 known to induce the formation of nitrenium ion. Unlike diazepine derivatives, the oxidative mixture had low impact on the affinity of oxa- and thiazepine derivatives such as loxapine, clothiapine or JL13 for the D2 receptor. Molecular docking simulations revealed a huge difference between the mode of interaction of clozapine nitrenium ion and the parent drug. Electronic and geometric changes of the tricyclic ring system caused by the oxidation appeared to prevent the compound finding the correct binding mode and could therefore explain the difference observed in binding affinities.
Laboratory of Medicinal Chemistry, Drug Research Center
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; fonds spéciaux pour la recherche ULg
Researchers ; Professionals ; Students

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