Novel drug developmental strategies for treatment-resistant depression

被引：63

作者：

Borbely, Eva ^{[1
,2
]}

Simon, Maria ^{[3
]}

Fuchs, Eberhard ^{[4
]}

Wiborg, Ove ^{[5
]}

Czeh, Boldizsar ^{[6
,7
]}

Helyes, Zsuzsanna ^{[1
,2
]}

机构：

[1] Univ Pecs, Med Sch, Dept Pharmacol & Pharmacotherapy, Pecs, Hungary

[2] Univ Pecs, Szentagothai Janos Res Ctr, Mol Pharmacol Res Grp, Pecs, Hungary

[3] Univ Pecs, Clin Ctr, Med Sch, Dept Psychiat & Psychotherapy, Pecs, Hungary

[4] Leibniz Inst Primate Res, German Primate Ctr, Gottingen, Germany

[5] Aalborg Univ, Dept Hlth Sci & Technol, Aalborg, Denmark

[6] Univ Pecs, Szentagothai Janos Res Ctr, Neurobiol Stress Res Grp, Pecs, Hungary

[7] Univ Pecs, Med Sch, Dept Lab Med, Pecs, Hungary

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2022年 / 179卷 / 06期

关键词：

antidepressant; glutamate; monoamine; neuroimaging; neuroinflammation; neuroplasticity; opioid; CONCISE GUIDE; MAJOR DEPRESSION; BOTULINUM-TOXIN; NMDA RECEPTOR; ANTIDEPRESSANT EFFICACY; RECURRENT DEPRESSION; CHANNEL BLOCKER; GUT MICROBIOTA; RODENT MODELS; ANIMAL-MODELS;

D O I：

10.1111/bph.15753

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Major depressive disorder is a leading cause of disability worldwide. Because conventional therapies are ineffective in many patients, novel strategies are needed to overcome treatment-resistant depression (TRD). Limiting factors of successful drug development in the last decades were the lack of (1) knowledge of pathophysiology, (2) translational animal models and (3) objective diagnostic biomarkers. Here, we review novel drug targets and drug candidates currently investigated in Phase I-III clinical trials. The most promising approaches are inhibition of glutamatergic neurotransmission by NMDA and mGlu(5) receptor antagonists, modulation of the opioidergic system by kappa receptor antagonists, and hallucinogenic tryptamine derivates. The only registered drug for TRD is the NMDA receptor antagonist, S-ketamine, but add-on therapies with second-generation antipsychotics, certain nutritive, anti-inflammatory and neuroprotective agents seem to be effective. Currently, there is an intense research focus on large-scale, high-throughput omics and neuroimaging studies. These results might provide new insights into molecular mechanisms and potential novel therapeutic strategies.

引用

页码：1146 / 1186

页数：41

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