Active metabolites as antidepressant drugs: the role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders
Identificadores
URI: http://hdl.handle.net/20.500.12020/754ISSN: 0028-3908
DOI: 10.3389/fpsyt.2013.00102
Fecha
2013-09-12Tipo de documento
articleÁrea/s de conocimiento
PsicologíaMateria/s Unesco
3201.05 Psicología ClínicaResumen
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.