Journal of Computer-Aided Molecular Design 2011-02-01

Interaction of clozapine and its nitrenium ion with rat D2 dopamine receptors: in vitro binding and computational study.

Sébastien Dilly, Jean-François Liégeois

Index: J. Comput. Aided Mol. Des. 25(2) , 163-9, (2011)

Full Text: HTML

Abstract

The interaction of diazepine analogues like clozapine or olanzapine with D2 receptor was greatly affected by a mixture of HRP/H(2)O(2) 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.

Related Compounds

  • Loxapine succinate

Related Articles:

Investigation of the disposition of loxapine, amoxapine and their hydroxylated metabolites in different brain regions, CSF and plasma of rat by LC–MS/MS

2012-01-01

[J. Pharm. Biomed. Anal. 58 , 83-93, (2012)]

In vitro aerosol characterization of Staccato(®) Loxapine.

2011-01-17

[Int. J. Pharm. 403(1-2) , 101-8, (2011)]

Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder.

2012-03-01

[Int. J. Clin. Pract. 66(3) , 318-25, (2012)]

The pharmacoepidemiology of antipsychotics for adults with schizophrenia in Canada, 2005 to 2009.

2011-10-01

[Can. J. Psychiatry. 56(10) , 630-4, (2011)]

The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

2012-03-01

[J. Pharmacol. Exp. Ther. 340(3) , 706-15, (2012)]

More Articles...