Glutamatergic Modulators for Rapid and Sustained Antidepressant Effect
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1. Realizations of non-commutative rational functions around a matrix centre,I:synthesis,minimal realizations and evaluation on stably finite algebras
2.Inflammation, stress and depression: An exploration of ketamine's therapeutic profile
- 关键词：
- Ketamine; depression; stress; inflammation; treatment-resistantdepression; anhedonia;TREATMENT-RESISTANT DEPRESSION; C-REACTIVE PROTEIN; NF-KAPPA-B;ANIMAL-MODELS; MICROGLIAL ACTIVATION; SERUM INTERLEUKIN-6; KYNURENINEPATHWAY; DOWN-REGULATION; DOUBLE-BLIND; GLUTAMATE
Well-established animal models of depression have described a proximal relationship between stress and central nervous system (CNS) inflammation - a relationship mirrored in the peripheral inflammatory biomarkers of individuals with depression. Evidence also suggests that stress-induced proin-flammatory states can contribute to the neurobiology of treatment-resistant depression. Interestingly, ketamine, a rapid-acting antidepressant, can partially exert its therapeu-tic effects via anti-inflammatory actions on the hypothala-mic-pituitary adrenal (HPA) axis, the kynurenine pathway or by cytokine suppression. Further investigations into the relationship between ketamine, inflammation and stress could provide insight into ketamine's unique therapeutic mechanisms and stimulate efforts to develop rapid-acting, anti-inflammatory-based antidepressants.
...3. Skorvanek M, Martinez-Martin P, Kovacs N, Zezula I, Rodriguez-Violante M, Corvol JC, Taba P, Seppi K, Levin O, Schrag A, Aviles-Olmos I, Alvarez-Sanchez M, Arakaki T, Aschermann Z, Benchetrit E, Benoit C, Bergareche-Yarza A, Cervantes-Arriaga A, Chade A, Cormier F, Datieva V, Gallagher DA, Garretto N, Gdovinova Z, Gershanik O, Grofik M, Han V, Kadastik-Eerme L, Kurtis MM, Mangone G, Martinez-Castrillo JC, Mendoza-Rodriguez A, Minar M, Moore HP, Muldmaa M, Mueller C, Pinter B, Poewe W, Rallmann K, Reiter E, Rodriguez-Blazquez C, Singer C, Valkovic P, Goetz CG, Stebbins GT\r\n (2018). Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients. Parkinsonism & Related Disorders, 52, 83−89. DOI: 10.1016/j.parkreldis.2018.03.027.
4.Authors' Reply to Pappagallo et al.: Comment on "Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status".
- 关键词：
- ;
5.Commentary on the Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder
- 关键词：
- ketamine; major depressive disorder; clinical practice guidelines
6.Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status
- 关键词：
- MAJOR DEPRESSIVE DISORDER; D-ASPARTATE ANTAGONIST; PROOF-OF-CONCEPT;TREATMENT-RESISTANT DEPRESSION; GAMMA-AMINOBUTYRIC-ACID; SITE PARTIALAGONIST; ADD-ON TRIAL; D-CYCLOSERINE; ANTIDEPRESSANT EFFICACY; RECEPTORANTAGONISTS
The efficacy of standard antidepressants is limited for many patients with mood disorders such as major depressive disorder (MDD) and bipolar depression, underscoring the urgent need to develop novel therapeutics. Both clinical and preclinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders. In particular, rapid reductions in depressive symptoms have been observed in response to subanesthetic doses of the glutamatergic modulator racemic (R,S)-ketamine in individuals with mood disorders. These results have prompted investigation into other glutamatergic modulators for depression, both as monotherapy and adjunctively. Several glutamate receptor-modulating agents have been tested in proof-of-concept studies for mood disorders. This manuscript gives a brief overview of the glutamate system and its relevance to rapid antidepressant response and discusses the existing clinical evidence for glutamate receptor-modulating agents, including (1) broad glutamatergic modulators ((R,S)-ketamine, esketamine, (R)-ketamine, (2R,6R)-hydroxynorketamine [HNK], dextromethorphan, Nuedexta [a combination of dextromethorphan and quinidine], deudextromethorphan [AVP-786], axsome [AXS-05], dextromethadone [REL-1017], nitrous oxide, AZD6765, CLE100, AGN-241751); (2) glycine site modulators (d-cycloserine [DCS], NRX-101, rapastinel [GLYX-13], apimostinel [NRX-1074], sarcosine, 4-chlorokynurenine [4-Cl-KYN/AV-101]); (3) subunit (NR2B)-specific N-methyl-d-aspartate (NMDA) receptor antagonists (eliprodil [EVT-101], traxoprodil [CP-101,606], rislenemdaz [MK-0657/CERC-301]); (4) metabotropic glutamate receptor (mGluR) modulators (basimglurant, AZD2066, RG1578, TS-161); and (5) mammalian target of rapamycin complex 1 (mTORC1) activators (NV-5138). Many of these agents are still in the preliminary stages of development. Furthermore, to date, most have demonstrated relatively modest effects compared with (R,S)-ketamine and esketamine, though some have shown more favorable characteristics. Of these novel agents, the most promising, and the ones for which the most evidence exists, appear to be those targeting ionotropic glutamate receptors.
...7.Reply to: "Letter to the Editor: Are ketamine-induced subjective bodily experiences associated with antidepressant effects? A sensation of floating and a sensation of Lightnessare not the same - A comment on Acevedo-Diaz et al." (Jpsychiatrres-D-21-00121)
8.Treatment of depression with ketamine does not change plasma levels of brain-derived neurotrophic factor or vascular endothelial growth factor
- 关键词：
- BIPOLAR DEPRESSION; RESISTANT; BDNF
9.Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants
- 关键词：
- Ketamine; serotonergic psychedelics; depression; glutamate; mechanism
Background: The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that "classic" serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period.Methods: This review summarizes areas of overlap between SP and ketamine research and considers the possibility of a common, downstream mechanism of action. The therapeutic relevance of the psychoactive state, overlapping cellular and molecular effects, and overlapping electrophysiological and neuroimaging observations are all reviewed.Results: Taken together, the evidence suggests a potentially shared mechanism wherein both ketamine and SPs may engender rapid neuroplastic effects in a glutamatergic activity-dependent manner. It is postulated that, though distinct, both ketamine and SPs appear to produce acute alterations in cortical network activity that may initially produce psychoactive effects and later produce milder, sustained changes in network efficiency associated with therapeutic response. However, despite some commonalities between the psychoactive component of these pharmacologically distinct therapies-such as engagement of the downstream glutamatergic pathway-the connection between psychoactive impact and antidepressant efficacy remains unclear and requires more rigorous research.Conclusions: Rapid-acting antidepressants currently under investigation may share some downstream pharmacological effects, suggesting that their antidepressant effects may come about via related mechanisms. Given the prototypic nature of ketamine research and recent progress in this area, this platform could be used to investigate entirely new classes of antidepressants with rapid and robust actions.
...10.Response to commentary on the comparative efficacy of esketamine vs. ketamine meta-analysis: Putting the cart before the horse?
- 关键词：
- TREATMENT-RESISTANT DEPRESSION