Front. Psychiatry, 12 September 2013 |

Active metabolites as antidepressant drugs: the role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders

  • 1Faculty of Health Sciences, Camilo José Cela University, Madrid, Spain
  • 2Department of Pharmacology, Faculty of Medicine, University of Alcalá, Madrid, Spain

Active metabolites of some antipsychotic drugs exhibit pharmacodynamic and pharmacokinetic properties that may be similar to or differ from the original compound and that can be translated by a different profile of responses and interactions to clinical level. Some of these antipsychotics’ active metabolites might participate in mechanisms of antidepressant activity, as m-chlorophenylpiperazine (aripiprazole), 9-OH-risperidone and norquetiapine. Norquetiapine exhibits distinct pharmacological activity from quetiapine and plays a fundamental role in its antidepressant efficacy. In this review, we analyze the differential pharmacological aspects between quetiapine and norquetiapine, both from the pharmacokinetic and pharmacodynamic perspectives (affinity for dopaminergic, noradrenegic, and/or serotonergic receptors, etc.), as well as differential neuroprotective role. The pharmacological differences between the two drugs could explain the differential clinical effect, as well as some differences in tolerability profile and drug interactions. The available data are sufficient to arrive at the conclusion that antidepressant activity of quetiapine is mediated, at least in part, by the active metabolite norquetiapine, which selectively inhibits noradrenaline reuptake, is a partial 5-HT1A receptor agonist, and acts as an antagonist at presynaptic α2, 5-HT2C, and 5-HT7 receptors.

Keywords: active metabolites, antipsychotic drugs, norquetiapine, quetiapine, mood disorders

Citation: López-Muñoz F and Álamo C (2013) Active metabolites as antidepressant drugs: the role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders. Front. Psychiatry 4:102. doi: 10.3389/fpsyt.2013.00102

Received: 28 February 2013; Accepted: 27 August 2013;
Published online: 12 September 2013.

Edited by:

Andrew C. McCreary, Brains On-Line, Netherlands

Reviewed by:

Adrian Newman-Tancredi, Neurolixis Inc., USA
Bart Ellenbroek, Victoria University Wellington, New Zealand

Copyright: © 2013 López-Muñoz and Álamo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Francisco López-Muñoz, Faculty of Health Sciences, Camilo José Cela University, C/Castillo de Alarcón, 49, Urb. Villafranca del Castillo, Villanueva de la Cañada, 28692 Madrid, Spain e-mail: