β_(2) and α_(2) adrenergic receptors mediate the proneurogenic in vitro effects of norquetiapine  

作　　者：Valeria Bortolotto Pier Luigi Canonico Mariagrazia Grilli 

机构地区：[1]Laboratory of Neuroplasticity,University of Piemonte Orientale,Novara,Italy [2]Department of Pharmaceutical Sciences,University of Piemonte Orientale,Novara,Italy

出　　处：《Neural Regeneration Research》2021年第10期2041-2047,共7页中国神经再生研究（英文版）

基　　金：This work was partially supported by the pharmaceutical company Astra Zeneca and by Fondazione Generali.

摘　　要：Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represents a therapeutic option in patients who are resistant to classical antidepressants,promotes adult hippocampal neurogenesis in preclinical studies.Norquetiapine,the key active metabolite of quetiapine in humans,has a distinctive receptor profile than the parent compound.The drug is indeed a high affinity norepinephrine transporter inhibitor and such activity has been proposed to contribute to its antidepressant effect.At present,no information is available on the effects of norquetiapine on adult neurogenesis.We extensively investigated the activity of quetiapine and norquetiapine on adult murine neural stem/progenitor cells and their progeny.Additionally,selective antagonists for β_(2)/α_(2) adrenergic receptors allowed us to evaluate if these receptors could mediate quetiapine and norquetiapine effects.We demonstrated that both drugs elicit in vitro proneurogenic effects but also that norquetiapine had distinctive properties which may depend on its ability to inhibit norepinephrine transporter and involve β_(2)/α_(2) adrenergic receptors.Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committees(IACUC)at University of Piemonte Orientale,Italy(approval No.1033/2015PR)on September 29,2015.

关 键 词：adrenergic receptors adult neurogenesis antidepressants ANTIPSYCHOTICS DEPRESSION neural progenitor cells norquetiapine QUETIAPINE 

分 类 号：R965[医药卫生—药理学]