scholarly journals Potentiation of Antidepressant Effects of Agomelatine and Bupropion by Hesperidin in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Jegan Sakthivel Nadar ◽  
Pravin Popatrao Kale ◽  
Pramod Kerunath Kadu ◽  
Kedar Prabhavalkar ◽  
Ruchita Dhangar
Keyword(s):  
Antidepressant Activity ◽  
Treated Group ◽  
Citrus Fruits ◽  
Fluorescence Detector ◽  
Treatment Of Depression ◽  
Antidepressant Effects ◽  
Antidepressant Efficacy ◽  
Flavanone Glycoside ◽  
Saline Vehicle ◽  
Immobility Period

Hesperidin, a well-known flavanone glycoside mostly found in citrus fruits, showed neuroprotective and antidepressant activity. Agomelatine, a melatonergic MT1/MT2 agonist and 5-HT2C receptor antagonist, exhibits good antidepressant efficacy. Bupropion has been widely used for the treatment of depression because of its dopamine and norepinephrine reuptake inhibition. The objective of present study was to assess the antidepressant effects of hesperidin combination with agomelatine or bupropion. Male Swiss Albino mice received treatment of saline, vehicle, ‘hesperidin alone’, ‘agomelatine alone’, hesperidin+agomelatine, ‘bupropion alone’, hesperidin+bupropion, and agomelatine+bupropion for 14 days. The immobility period was analysed 30 min after the treatment in forced swim and tail suspension tests. Dopamine and serotonin levels were analysed in hippocampus, cerebral cortex, and whole brain using HPLC with fluorescence detector. Hesperidin plus agomelatine treated group was better in terms of decrease in immobility period and increase in dopamine and serotonin levels when compared to their respective monotherapy treated groups.

Neurotrophic Properties of Silexan, an Essential Oil from the Flowers of Lavender-Preclinical Evidence for Antidepressant-Like Properties

2020 ◽  
Vol 54 (01) ◽  
pp. 37-46
Author(s):  
Kristina Friedland ◽  
Giacomo Silani ◽  
Anita Schuwald ◽  
Carola Stockburger ◽  
Egon Koch ◽  
...  
Keyword(s):  
Essential Oil ◽  
Hippocampal Neurons ◽  
Day Treatment ◽  
Neuronal Cell ◽  
Antidepressant Activity ◽  
In Vivo Models ◽  
Antidepressant Effects ◽  
Primary Hippocampal Neurons

Abstract Background Silexan, a special essential oil from flowering tops of lavandula angustifolia, is used to treat subsyndromal anxiety disorders. In a recent clinical trial, Silexan also showed antidepressant effects in patients suffering from mixed anxiety-depression (ICD-10 F41.2). Since preclinical data explaining antidepressant properties of Silexan are missing, we decided to investigate if Silexan also shows antidepressant-like effects in vitro as well as in vivo models. Methods We used the forced swimming test (FST) in rats as a simple behavioral test indicative of antidepressant activity in vivo. As environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology—resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function—we investigated the neurotrophic properties of Silexan in neuronal cell lines and primary hippocampal neurons. Results The antidepressant activity of Silexan (30 mg/kg BW) in the FST was comparable to the tricyclic antidepressant imipramine (20 mg/kg BW) after 9-day treatment. Silexan triggered neurite outgrowth and synaptogenesis in 2 different neuronal cell models and led to a significant increase in synaptogenesis in primary hippocampal neurons. Silexan led to a significant phosphorylation of protein kinase A and subsequent CREB phosphorylation. Conclusion Taken together, Silexan demonstrates antidepressant-like effects in cellular as well as animal models for antidepressant activity. Therefore, our data provides preclinical evidence for the clinical antidepressant effects of Silexan in patients with mixed depression and anxiety.

scholarly journals Therapeutic Potential of Hericium erinaceus for Depressive Disorder

2019 ◽  
Vol 21 (1) ◽  
pp. 163 ◽  
Author(s):  
Pit Shan Chong ◽  
Man-Lung Fung ◽  
Kah Hui Wong ◽  
Lee Wei Lim
Keyword(s):  
Depressive Disorder ◽  
Disease Burden ◽  
Therapeutic Potential ◽  
Fruiting Bodies ◽  
Hericium Erinaceus ◽  
Treatment Of Depression ◽  
Antidepressant Effects ◽  
Potential Benefits ◽  
Potential Alternative ◽  
Global Disease Burden

Depression is a common and severe neuropsychiatric disorder that is one of the leading causes of global disease burden. Although various anti-depressants are currently available, their efficacies are barely adequate and many have side effects. Hericium erinaceus, also known as Lion’s mane mushroom, has been shown to have various health benefits, including antioxidative, antidiabetic, anticancer, anti-inflammatory, antimicrobial, antihyperglycemic, and hypolipidemic effects. It has been used to treat cognitive impairment, Parkinson’s disease, and Alzheimer’s disease. Bioactive compounds extracted from the mycelia and fruiting bodies of H. erinaceus have been found to promote the expression of neurotrophic factors that are associated with cell proliferation such as nerve growth factors. Although antidepressant effects of H. erinaceus have not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression, H. erinaceus may be a potential alternative medicine for the treatment of depression. This article critically reviews the current literature on the potential benefits of H. erinaceus as a treatment for depressive disorder as well as its mechanisms underlying the antidepressant-like activities.

scholarly journals Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine

2018 ◽  
Vol 33 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Jaclyn N Highland ◽  
Patrick J Morris ◽  
Panos Zanos ◽  
Jacqueline Lovett ◽  
Soumita Ghosh ◽  
...  
Keyword(s):  
Oral Administration ◽  
Learned Helplessness ◽  
Oral Bioavailability ◽  
Forced Swim Test ◽  
Abuse Potential ◽  
Absolute Bioavailability ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Antidepressant Efficacy

Background: ( R,S)-ketamine has gained attention for its rapid-acting antidepressant actions in patients with treatment-resistant depression. However, widespread use of ketamine is limited by its side effects, abuse potential, and poor oral bioavailability. The ketamine metabolite, ( 2R,6R)-hydroxynorketamine, exerts rapid antidepressant effects, without ketamine’s adverse effects and abuse potential, in rodents. Methods: We evaluated the oral bioavailability of ( 2R,6R)-hydroxynorketamine in three species (mice, rats, and dogs) and also evaluated five candidate prodrug modifications for their capacity to enhance the oral bioavailability of ( 2R,6R)-hydroxynorketamine in mice. Oral administration of ( 2R,6R)-hydroxynorketamine was assessed for adverse behavioral effects and for antidepressant efficacy in the mouse forced-swim and learned helplessness tests. Results: ( 2R,6R)-hydroxynorketamine had absolute bioavailability between 46–52% in mice, 42% in rats, and 58% in dogs. Compared to intraperitoneal injection in mice, the relative oral bioavailability of ( 2R,6R)-hydroxynorketamine was 62%, which was not improved by any of the candidate prodrugs tested. Following oral administration, ( 2R,6R)-hydroxynorketamine readily penetrated the brain, with brain to plasma ratios between 0.67–1.2 in mice and rats. Oral administration of ( 2R,6R)-hydroxynorketamine to mice did not alter locomotor activity or precipitate behaviors associated with discomfort, sickness, or stereotypy up to a dose of 450 mg/kg. Oral ( 2R,6R)-hydroxynorketamine reduced forced-swim test immobility time (15–150 mg/kg) and reversed learned helplessness (50–150 mg/kg) in mice. Conclusions: These results demonstrate that ( 2R,6R)-hydroxynorketamine has favorable oral bioavailability in three species and exhibits antidepressant efficacy following oral administration in mice.

scholarly journals Rapid-Acting Antidepressant Therapies

2018 ◽  
Author(s):  
Bashkim Kadriu ◽  
Subha Subramanian ◽  
Zhi-De Deng ◽  
Ioline D. Henter ◽  
Lawrence T. Park ◽  
...  
Keyword(s):  
Rapid Onset ◽  
Emergency Setting ◽  
Glutamatergic System ◽  
Major Depressive ◽  
Signaling Systems ◽  
Antidepressant Effects ◽  
Remission Rates ◽  
Electrophysiological Studies ◽  
Antidepressant Efficacy ◽  
Neural Signaling

Major depressive disorder (MDD) is a highly prevalent and debilitating illness and closely linked to suicide risk. Currently available antidepressants take weeks to work and have low remission rates; indeed, about a third of individuals with MDD fail to fully remit in response to these agents. Novel therapies that target the glutamatergic system—such as ketamine—offer rapid antidepressant effects as well as high remission rates, making them attractive therapeutic options. This chapter reviews the evidence for the antidepressant efficacy of several novel therapeutics, including ketamine, esketamine, nitrous oxide, scopolamine, GLYX-13, and buprenorphine, as well as interventional techniques such as sleep deprivation. Notably, ketamine and esketamine also rapidly reduce suicidal thoughts, making them attractive solutions in an emergency setting. Because studying the rapid onset of antidepressant effects associated with these agents has also improved our understanding of the neurocircuitry and neural signaling systems underlying MDD, some pivotal drug trials using rodents, neuroimaging, and electrophysiological studies are also reviewed.

scholarly journals Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1361 ◽  
Author(s):  
Dylan O’Neill Rothenberg ◽  
Lingyun Zhang
Keyword(s):  
Antidepressant Activity ◽  
Black Tea ◽  
Tea Consumption ◽  
Major Pathway ◽  
Depression Risk ◽  
Microbiome Diversity ◽  
Antidepressant Effects ◽  
Bdnf Signaling ◽  
Risk Ratios

This article is a comprehensive review of the literature pertaining to the antidepressant effects and mechanisms of regular tea consumption. Meta-data supplemented with recent observational studies were first analyzed to assess the association between tea consumption and depression risk. The literature reported risk ratios (RR) were 0.69 with 95% confidence intervals of 0.62–0.77. Next, we thoroughly reviewed human trials, mouse models, and in vitro experiments to determine the predominant mechanisms underlying the observed linear relationship between tea consumption and reduced risk of depression. Current theories on the neurobiology of depression were utilized to map tea-mediated mechanisms of antidepressant activity onto an integrated framework of depression pathology. The major nodes within the network framework of depression included hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, inflammation, weakened monoaminergic systems, reduced neurogenesis/neuroplasticity, and poor microbiome diversity affecting the gut–brain axis. We detailed how each node has subsystems within them, including signaling pathways, specific target proteins, or transporters that interface with compounds in tea, mediating their antidepressant effects. A major pathway was found to be the ERK/CREB/BDNF signaling pathway, up-regulated by a number of compounds in tea including teasaponin, L-theanine, EGCG and combinations of tea catechins and their metabolites. Black tea theaflavins and EGCG are potent anti-inflammatory agents via down-regulation of NF-κB signaling. Multiple compounds in tea are effective modulators of dopaminergic activity and the gut–brain axis. Taken together, our findings show that constituents found in all major tea types, predominantly L-theanine, polyphenols and polyphenol metabolites, are capable of functioning through multiple pathways simultaneously to collectively reduce the risk of depression.

The paradox of tianeptine

1993 ◽  
Vol 8 (S2) ◽  
pp. 89s-93s ◽  
Author(s):  
M Ansseau
Keyword(s):  
Chronic Conditions ◽  
Depressive Disorders ◽  
Antidepressant Activity ◽  
Synaptic Cleft ◽  
Human Platelets ◽  
Mechanisms Of Action ◽  
Functional Deficit ◽  
Number Of Patients ◽  
Biochemical Studies ◽  
Antidepressant Efficacy

SummaryThe classical biochemical hypothesis of depression posits a functional deficit in central neurotransmitter systems, particularly serotonin (5-HT) and/or noradrenaline. The major support for this theory was that antidepressants increase the amount of neurotransmitters in the synaptic cleft, by inhibiting reuptake mechanisms (tricyclics) or inhibiting enzymatic catabolism (MAOIs). The major role suggested for 5-HT in this theory led to the development of a large number of compounds which selectively inhibit 5-HT reuptake, such as fluvoxamine, fluoxetine, citalopram, sertraline, paroxetine, etc. Numerous clinical studies have demonstrated the antidepressant activity of such types of agents, supporting 5-HT deficit as the main origin of depression. Tianeptine is active in classical animal models of antidepressants. Its antidepressant efficacy has been established in controlled trials involving a large number of patients. Several biochemical studies however demonstrated that tianeptine induces in acute as well as in chronic conditions, a presynaptic increase of 5-HT reuptake, both in animal and human platelets and animal CNS. Therefore, as a 5-HT reuptake enhancer, tianeptine exhibits a mechanism of action totally opposite to 5-HT reuptake blockers such as fluoxetine but, paradoxically, both mechanisms of action are associated with a therapeutic activity in depressive disorders. Several hypotheses to explain these paradoxical findings and different methodologies to test them clinically are proposed.

scholarly journals Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants

2020 ◽  
Author(s):  
Bashkim Kadriu ◽  
Maximillian Greenwald ◽  
Ioline D Henter ◽  
Jessica R Gilbert ◽  
Christoph Kraus ◽  
...  
Keyword(s):  
Therapeutic Response ◽  
Network Activity ◽  
Dependent Manner ◽  
Network Efficiency ◽  
Rigorous Research ◽  
Antidepressant Effects ◽  
Psychoactive Effects ◽  
Antidepressant Efficacy ◽  
Molecular Effects ◽  
Activity Dependent

Abstract 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.

Everyday Problems in Treating Depression: Focus on SNRIs

CNS Spectrums ◽  
2008 ◽  
Vol 13 (S11) ◽  
pp. 4-4 ◽  
Author(s):  
Siegfried Kasper
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Antidepressant Activity ◽  
New Class ◽  
Treatment Of Depression ◽  
Norepinephrine Reuptake Inhibitor ◽  
Dual Action ◽  
Everyday Problems ◽  
Serotonin Norepinephrine Reuptake Inhibitor ◽  
Poor Tolerability ◽  
Norepinephrine Reuptake

Most effective antidepressants directly or indirectly increase the synaptic concentrations of serotonin (5-HT) and/or norepinephrine (NE) by blocking the reuptake of one or both of the neurotransmitters. This property was initially discovered with the tricyclic antidepressants (TCAs). Their various additional interactions at different receptors and ion channels are not required for antidepressant action, but are responsible for the poor tolerability and toxicity in overdose of the early antidepressants.The selective serotonin reuptake inhibitors are effective and well tolerated. Selective norepinephrine reuptake inhibitors, such as reboxetine, also have proven antidepressant activity. A selective action on one or the other of the principal monoamines thus appears to be sufficient for antidepressant activity. The idea that a dual action on both neurotransmitters might produce greater efficacy in certain patients led to the development of the serotonin norepinephrine reuptake inhibitor (SNRI) antidepressants, which block the reuptake of both 5-HT and NE without the nonspecific, side-effect–inducing interactions of the TCAs. The three SNRIs—venlafaxine, milnacipran, and duloxetine—constitute a new class of antidepressants.Antidepressant response rates rarely exceed 60% to 70% and remission rates are usually <50%. Although SNRIs clearly provide superior efficacy in certain populations, their use has not dramatically changed antidepressant therapy. The search for agents that are more effective, rapidly acting, and better tolerated continues. However, clinicians must find ways to better use the antidepressants that are available today. This supplement, based on a symposium held at the International Forum on Affective Disorders in Budapest in December 2007, discusses several everyday problems in the treatment of depression, with a focus on SNRIs.

SS05-02 - Management of depression with agomelatine: A different perception

2011 ◽  
Vol 26 (S2) ◽  
pp. 2178-2178
Author(s):  
G. Hajak
Keyword(s):  
Side Effects ◽  
Antidepressant Treatment ◽  
Real Life ◽  
Daily Practice ◽  
Early Improvement ◽  
Real Life Setting ◽  
Treatment Of Depression ◽  
Perceived Benefit ◽  
Antidepressant Efficacy ◽  
Clinical Benefits

Agomelatine is a completely new approach to the treatment of depression thanks to its innovative mode of action. Acting as melatonergic agonist and 5-HT2C antagonist, it provides depressed patients with a distinctive antidepressant efficacy that perfectly suits patients’ needs and addresses all symptoms at each step of depression. Two years after the first launch in Europe, now is the time for an update from doctors and patients alike.The patient/doctor relation is key when initiating depression treatment, because patients are reluctant to start, fearing withdrawal symptoms, serious unwanted side effects, and “addiction”. It is important therefore that they understand that agomelatine has none of these effects.The benefits perceived by patients right from the first days of treatment are influential, because patients are reluctant to continue with classic antidepressants (delayed onset of perceived benefit, early side effects). The early improvement reported by patients on agomelatine supplements data on clinical benefits seen in clinical trials from the first week versus venlafaxine (CGI-I, rate of response, daytime alertness, feeling good) and after two weeks versus sertraline (twice as many HAM-D responders to agomelatine as to sertraline).Finally, patients are reluctant to maintain antidepressant treatment because of later side effects (weight gain, sexual dysfunction, emotional blunting). Patients on agomelatine confirm the absence of the classic side effects of antidepressants and are more likely to continue treatment than they are with other drugs. Both the antidepressant efficacy and the tolerability were confirmed in a large non-interventional study in a real-life setting in daily practice.

scholarly journals Antidepressant effects of natural and micropropagated Bacopa monnieri (L.) plant extracts

2021 ◽  
Vol 8 (2) ◽  
pp. 141-145
Author(s):  
Firoj A Tamboli ◽  
Vinod D Rangari ◽  
Harinath N More ◽  
Vijay H Kutwade ◽  
Vivek M Patil
Keyword(s):  
Locomotor Activity ◽  
Motor Activity ◽  
Plant Extract ◽  
Antidepressant Activity ◽  
Spontaneous Motor Activity ◽  
P Value ◽  
Standard Drug ◽  
Antidepressant Effects ◽  
Different Doses ◽  
Micropropagated Plant

Linn. an important medicinal plant in Indian system of alternative medicine belonging to Scrophulariaceae family. It is distributed in the wet and marshy lands throughout India, Nepal and many other parts of world. This study was carried out to evaluate the natural and micropropagated plant extract for antidepressant activity. Antidepressant effects of natural and micropropagated plant extract was evaluated by spontaneous motor activity. All the extracts were administered 30 min prior to the test. The standard drug chlorpromazine (2mg/kg) was used. The locomotor activity was performed using an actophotometer after different doses of test drug. Result: The locomotor activity of control and treated mice were recorded and statistically correlated among the control, standard and the test drugs. The inhibition of spontaneous motor activity in case of BMN, BMS extract was found 291, 93.5 and 277, 93.66 count at interval of 30 and 60 min. respectively. But in case of BMM plant extract it was found 290, 87.33 and 146 count at 30, 60 and 120 min. interval respectively so results showed that a significant antidepressant-like effect at a dose of 100 mg/kg. It can be used as adjuvant therapy for depression. There was statistically highly significant (p value &#60;0.001) association observed. Further evaluation on the different mechanisms of action of ethanolic extracts of natural and micropropagated plant needs to be studied in the future.

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