Perspectives for therapy of treatment‐resistant depression

Papp, Mariusz; Cubała, Wiesław Jerzy; Święcicki, Łukasz; Newman‐Tancredi, Adrian; Willner, Paul

doi:10.1111/bph.15596

Cited by 49 publications

(35 citation statements)

References 171 publications

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“…Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors and some atypical agents are the antidepressant drug groups used in the treatment of depressive disorders today (Marasine et al, 2021). However, a significant proportion of patients with depression either does not respond adequately to these drugs or cannot tolerate various drug-induced side effects (Papp et al, 2021). Therefore, research on the discovery and development of more effective and safer antidepressants is ongoing.…”

Section: Introductionmentioning

confidence: 99%

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

et al. 2022

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Background: Depression is a disease that affects millions of people worldwide, and the discovery and development of effective and safe antidepressant drugs is one of the important topics of psychopharmacology. Objectives: In this study, it was aimed to investigate the antidepressant-like activity potential of tofisopam, an anxiolytic drug with 2,3-benzodiazepine structure, and to elucidate the pharmacological mechanisms mediating this effect. Methods: The antidepressant-like activity of tofisopam was investigated using tail suspension and modified forced swimming tests. Possible interactions of tofisopam with µ- and δ-opioid receptor subtypes were clarified by pharmacological antagonism, molecular docking and molecular dynamics simulation studies. Results: Tofisopam (50 and 100 mg/kg) significantly shortened the immobility time of mice in both the tail suspension and the modified forced swimming tests. The drug, at the same doses, prolonged the duration of swimming and climbing behaviours measured in modified forced swimming tests. A dosage of 25 mg/kg was ineffective. Mechanistic studies showed that the pretreatment with p-chlorophenylalanine methyl ester (serotonin synthesis inhibitor; 4 consecutive days, 100 mg/kg), α-methyl-para-tyrosine methyl ester (catecholamine synthesis inhibitor; 100 mg/kg), naloxonazine (selective µ-opioid receptor blocker, 7 mg/kg) and naltrindole (a selective δ-opioid receptor blocker, 0.99 mg/kg) abolished the anti-immobility effect induced by the 50 mg/kg dose of tofisopam in the tail suspension tests. Our in silico studies supported the behavioural findings that the antidepressant-like effect of tofisopam is mediated by μ- and δ-opioid receptors. Conclusion: This study is the first to show that tofisopam has antidepressant-like activity mediated by the serotonergic, catecholaminergic and opioidergic systems.

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Section: Introductionmentioning

confidence: 99%

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

et al. 2022

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“…Ketamine and its FDA-approved enantiomer, esketamine, have demonstrated their efficacy and are usually well tolerated at the doses used as antidepressant. Although there may be some concerns about the appearance of psychotomimetic effects and other adverse reactions, these have been described only in a low percentage of patients or with very high doses that are administered for prolonged periods ( 61 , 62 ). Therefore, these findings provide valuable information to consider in the development of new and improved antidepressant drugs ( 42 , 43 , 61 ).…”

Section: Mechanisms Of Action Involved In the Antidepressant Effectmentioning

confidence: 99%

3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs

et al. 2022

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The utility of classical drugs used to treat psychiatric disorders (e.g., antidepressants, anxiolytics) is often limited by issues of lack of efficacy, delayed onset of action or side effects. Psychoactive substances have a long history of being used as tools to alter consciousness and as a gateway to approach the unknown and the divinities. These substances were initially obtained from plants and animals and more recently by chemical synthesis, and its consumption evolved toward a more recreational use, leading to drug abuse-related disorders, trafficking, and subsequent banning by the authorities. However, these substances, by modulation of certain neurochemical pathways, have been proven to have a beneficial effect on some psychiatric disorders. This evidence obtained under medically controlled conditions and often associated with psychotherapy, makes these substances an alternative to conventional medicines, to which in many cases the patient does not respond properly. Such disorders include post-traumatic stress disease and treatment-resistant depression, for which classical drugs such as MDMA, ketamine, psilocybin and LSD, among others, have already been clinically tested, reporting successful outcomes. The irruption of new psychoactive substances (NPS), especially during the last decade and despite their recreational and illicit uses, has enlarged the library of substances with potential utility on these disorders. In fact, many of them were synthetized with therapeutic purposes and were withdrawn for concrete reasons (e.g., adverse effects, improper pharmacological profile). In this review we focus on the basis, existing evidence and possible use of synthetic cathinones and psychedelics (specially tryptamines) for the treatment of mental illnesses and the properties that should be found in NPS to obtain new therapeutic compounds.

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“…This approach may reveal future predictive biomarkers for the pharmacological treatment and prognosis of stress‐related disorders. The current status of treatment‐resistant depression in a wide spectrum of laboratory models and its pharmacological modalities is reviewed by Papp et al (2022). The authors discuss both pharmacological (novel rapidly acting antidepressants targeting glutamate receptors or 5‐HT 1A receptors) and non‐pharmacological (deep brain stimulation) strategies to treat people with major depressive disorders who do not respond adequately to a course of appropriate antidepressants.…”

Section: Linked Articlesmentioning

confidence: 99%