-
Steroids Aug 2022Mifepristone is a non-selective progesterone (PR), glucocorticoid (GR), and androgen receptor (AR) antagonist with antidepressant and anxiolytic effects. The dose and... (Review)
Review
Mifepristone is a non-selective progesterone (PR), glucocorticoid (GR), and androgen receptor (AR) antagonist with antidepressant and anxiolytic effects. The dose and duration of mifepristone administration vary in rodent preclinical studies to evaluate depression-like and anxiety-like behavior. This review summarizes the findings so far and attempts to reconcile some of the differences in the results. While a few studies assessed basal depression- and anxiety-like behavior, several studies have used mifepristone in conjunction with stress, corticosterone/dexamethasone (after adrenalectomy), or progesterone administration. The effect of mifepristone on depression-like behavior appears to depend not only on the dose and duration of administration but also on the intensity or type of stress. In addition, the anxiolytic effects may depend on the species and strain of the experimental animals. More reports assess antidepressant-like or anxiolytic-like effects following acute than chronic administration. These effects are dependent on the paradigms and the nature of stressors. Most mifepristone studies implicate the role of GRs, yet only two reports have confirmed its role using a genetic approach, whereas none implicate the role of PRs/ARs. There are several novel selective GR antagonists whose effects on depression- and anxiety-like behavior are yet to be studied. Future studies could aim to confirm the role of GRs and evaluate the contribution of PRs/ARs to the effects of mifepristone. Such studies will contribute to a better understanding of depression, anxiety, and other mood disorders and develop novel strategies, particularly for treatment-resistant conditions.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Depression; Glucocorticoids; Mifepristone; Progesterone; Receptors, Glucocorticoid; Rodentia
PubMed: 35679911
DOI: 10.1016/j.steroids.2022.109058 -
Molecular Psychiatry Jan 2022Behavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade,... (Review)
Review
Behavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade, several of them were translated to humans with three clinically relevant goals: to assess potential efficacy of candidate treatments in healthy humans; to develop diagnostic tests or biomarkers; and to elucidate the pathophysiology of anxiety disorders. In this review, we scrutinise these promises and compare seven anxiety tests that are validated across species: five approach-avoidance conflict tests, unpredictable shock anticipation, and the social intrusion test in children. Regarding the first goal, three tests appear suitable for anxiolytic drug screening in humans. However, they have not become part of the drug development pipeline and achieving this may require independent confirmation of predictive validity and cost-effectiveness. Secondly, two tests have shown potential to measure clinically relevant individual differences, but their psychometric properties, predictive value, and clinical applicability need to be clarified. Finally, cross-species research has not yet revealed new evidence that the physiology of healthy human behaviour in anxiety tests relates to the physiology of anxiety symptoms in patients. To summarise, cross-species anxiety tests could be rendered useful for drug screening and for development of diagnostic instruments. Using these tests for aetiology research in healthy humans or animals needs to be queried and may turn out to be unrealistic.
Topics: Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Humans; Psychiatry; Psychometrics
PubMed: 34561614
DOI: 10.1038/s41380-021-01299-4 -
Journal of Basic and Clinical... Mar 2017
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Disease Models, Animal; Drug Evaluation, Preclinical; Hypnosis; Hypnotics and Sedatives; Mice; Plant Preparations; Rats
PubMed: 28284033
DOI: 10.1515/jbcpp-2017-0022 -
Pharmacological Research Jul 2021The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAR), and the down-regulation of its... (Review)
Review
The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAR), and the down-regulation of its biosynthesis have been attributed to the development of mood disorders, such as depression, anxiety and post-traumatic stress disorder (PTSD). ALLO mediated depression/anxiety involves GABAergic mechanisms and appears to be related to brain-derived neurotrophic factor (BDNF), dopamine receptor, glutamate neurotransmission, and Ca channel. In the clinical, brexanolone, as a newly developed intravenous ALLO preparation, has been approved for the treatment of postpartum depression (PPD). In addition, traditional antidepressants such as selective serotonin reuptake inhibitor (SSRI) could reverse ALLO decline. Recently, the translocation protein (TSPO, 18 kDa), which involves in the speed-limiting step of ALLO synthesis, and ALLO derivatization have been identified as new directions for antidepressant therapy. This review provides an overview of ALLO researches in animal model and patients, discusses its role in the development and treatment of depression/anxiety, and directs its therapeutic potential in future.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Depression; Humans; Mood Disorders; Pregnanolone; Receptors, GABA-A
PubMed: 34019980
DOI: 10.1016/j.phrs.2021.105682 -
Central Nervous System Agents in... 2023is a native plant that is commonly mentioned in Ayurveda as a Rasayana and is primarily recommended for use in mental stimulation and rejuvenation therapy. is used as...
BACKGROUND
is a native plant that is commonly mentioned in Ayurveda as a Rasayana and is primarily recommended for use in mental stimulation and rejuvenation therapy. is used as a brain tonic. The plant is reported to be a prominent memory-improving drug. It is used as a psychostimulant and tranquilizer. It is reported to reduce mental tension.
OBJECTIVE
The present study aimed to explore the protective effect of hydroalcoholic extract from the leaves of along with CNS depressant and anti-anxiety activities, in models of mice.
METHODS
The extract from leaves of were sequentially isolated with a mixture of water and alcohol solution in the soxhlet apparatus. An acute toxicity study was conducted as per OECD guidelines no. 423, in which 18 Albino male mice were treated with different doses (1, 10, 100, 500, 1000, and 2000 mg/kg) of hydroalcoholic extract of and assessed for toxicity parameters for 14 days. Various psychomotor activities of hydroalcoholic extract from leaves of for 100, 200, and 300 mg/kg doses were performed in mice by using various tests like actophotometer, open field, rota-rod, grip strength tests, elevated plus maze, hole board test, inclined plane, chimney test.
RESULTS
The hydroalcoholic extract from leaves of was found to fall under category 4 in the acute toxicity study. Therefore, 100, 200, and 300 mg/kg doses of hydroalcoholic extract of leaves of were selected for the further pharmacological study. The results of psychomotor tests (actophotometer, open field, rota-rod, grip strength, hole board test, inclined plane, chimney test, elevated plus maze, light-dark model) for test doses 100, 200, and 300 in mice showed CNS depressant and anti-anxiety effects.
CONCLUSION
Hydroalcoholic extract from leaves of at the 100, 200, and 300 mg/kg doses has shown CNS depressant and anti-anxiety effects in mice models.
Topics: Mice; Animals; Convolvulus; Plant Extracts; Anti-Anxiety Agents; Central Nervous System Depressants; Plant Leaves
PubMed: 36825716
DOI: 10.2174/1871524923666230220144640 -
European Neuropsychopharmacology : the... Jul 2023The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed the evidence for... (Meta-Analysis)
Meta-Analysis Review
The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed the evidence for anxiety-reduction by compounds that facilitate endocannabinoid signaling in humans and animals. To identify areas of specific potential, effects of moderators were assessed. Literature was searched in Pubmed and Embase up to May 2021. A placebo/vehicle-control group was required and in human studies, randomization. We excluded studies that co-administered other substances. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. We conducted three-level random effects meta-analyses and explored sources of heterogeneity using Bayesian regularized meta-regression (BRMA). The systematic review yielded 134 studies. We analyzed 120 studies (114 animal, 6 human) that investigated cannabidiol (CBD, 61), URB597 (39), PF-3845 (6) and AM404 (14). Pooled effects on conditioned and unconditioned anxiety in animals (with the exception of URB597 on unconditioned anxiety) and on experimentally induced anxiety in humans favored the investigational drugs over placebo/vehicle. Publication year was negatively associated with effects of CBD on unconditioned anxiety. Compared to approach avoidance tests, tests of repetitive-compulsive behavior were associated with larger effects of CBD and URB597, and the social interaction test with smaller effects of URB597. Larger effects of CBD on unconditioned anxiety were observed when anxiety pre-existed. Studies reported few side effects at therapeutic doses. The evidence quality was low with indications of publication bias. More clinical trials are needed to translate the overall positive results to clinical applications.
Topics: Animals; Humans; Anti-Anxiety Agents; Endocannabinoids; Bayes Theorem; Anxiety; Cannabidiol
PubMed: 37094409
DOI: 10.1016/j.euroneuro.2023.04.001 -
Irish Journal of Psychological Medicine Mar 2020Sexual side effects have rarely been reported secondary to treatment with Pregabalin, a structural analogue of the inhibitory neurotransmitter gamma amino butyric acid...
INTRODUCTION
Sexual side effects have rarely been reported secondary to treatment with Pregabalin, a structural analogue of the inhibitory neurotransmitter gamma amino butyric acid (GABA).
METHOD
We present the case of AB, a 27-year-old single man with a diagnosis of recurrent depressive disorder who was prescribed pregabalin to alleviate the significant anxiety symptoms he was experiencing.
RESULTS
A significant amelioration in anxiety symptoms was attained; however, he developed the adverse effects of acute sexual disinhibition and increased libido. These adverse effects were temporally related to treatment with pregabalin and reduced with dose reduction of this agent.
CONCLUSIONS
To date, limited published data are available relating such a reaction to pregabalin. A greater clinical recognition of this association between pregabalin and sexual disinhibition, would allow clinicians to intervene at an earlier stage of this adverse effect and potentially as in this case, management may only require dose reduction rather than treatment discontinuation.
Topics: Adult; Anti-Anxiety Agents; Depressive Disorder; Humans; Libido; Pregabalin
PubMed: 32223791
DOI: 10.1017/ipm.2017.5 -
Expert Review of Neurotherapeutics Nov 2014Benzodiazepines (BDZs) continue to be shrouded in controversy, mainly because of dependence associated with their long-term use and some of their side effects. Despite... (Review)
Review
Benzodiazepines (BDZs) continue to be shrouded in controversy, mainly because of dependence associated with their long-term use and some of their side effects. Despite treatment recommendations favoring newer antidepressants, BDZs are still commonly prescribed for anxiety and related disorders. Recent studies have demonstrated that long-term use of BDZs for these conditions can be effective and safe and that BDZs can be combined with psychological therapy and antidepressants to produce optimal outcomes. Such findings, along with a failure to convincingly demonstrate the overall superiority of alternative pharmacotherapy for anxiety and related disorders, have given an impetus to a reconsideration of the role of BDZs. This article reviews BDZs and other pharmacotherapy options for anxiety and related disorders and suggests that treatment guidelines should acknowledge that BDZs can be used as first-line, long-term pharmacological treatment for panic disorder, generalized anxiety disorder and social anxiety disorder.
Topics: Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Benzodiazepines; Humans
PubMed: 25242262
DOI: 10.1586/14737175.2014.963057 -
Fundamental & Clinical Pharmacology Jun 2016Anxiety and depression are complex heterogeneous psychiatric disorders and leading causes of disability worldwide. This review summarizes reports on the fundamentals,... (Review)
Review
Anxiety and depression are complex heterogeneous psychiatric disorders and leading causes of disability worldwide. This review summarizes reports on the fundamentals, prevalence, diagnosis, neurobiology, advancement in treatment of these diseases and preclinical assessment of botanicals. This review was conducted through bibliographic investigation of scientific journals, books, electronic sources, unpublished theses and electronic medium such as ScienceDirect and PubMed. A number of the first-line drugs (benzodiazepine, azapirone, antidepressant tricyclics, monoamine oxidase inhibitors, serotonin selective reuptake inhibitors, noradrenaline reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, etc.) for the treatment of these psychiatric disorders are products of serendipitous discoveries. Inspite of the numerous classes of drugs that are available for the treatment of anxiety and depression, full remission has remained elusive. The emerging clinical cases have shown increasing interests among health practitioners and patients in phytomedicine. The development of anxiolytic and antidepressant drugs of plant origin takes advantage of multidisciplinary approach including but not limited to ethnopharmacological survey (careful investigation of folkloric application of medicinal plant), phytochemical and pharmacological studies. The selection of a suitable plant for a pharmacological study is a basic and very important step. Relevant clues to achieving this step include traditional use, chemical composition, toxicity, randomized selection or a combination of several criteria. Medicinal plants have been and continue to be a rich source of biomolecule with therapeutic values for the treatment of anxiety and depression.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Depression; Humans; Plant Extracts; Plants, Medicinal; Treatment Outcome
PubMed: 26851117
DOI: 10.1111/fcp.12186 -
Biomedicine & Pharmacotherapy =... Jan 2019Anxiety and depression, the most prevalent psychiatric disorders are co-morbid in nature affecting several people across the world. There is an increase in demand for... (Review)
Review
Anxiety and depression, the most prevalent psychiatric disorders are co-morbid in nature affecting several people across the world. There is an increase in demand for complementary and alternative medicines, specifically herbal botanicals due to various side effects exhibited by conventional drugs. Herbal drugs mentioned in traditional medicines, face acceptance issues by the medical community due to lack of scientific data regarding their neurochemical pathways. Hence, there has been an increased interest in the quest to unravel the mechanisms of action of herbal psychotropics. With the advancements in "omic technologies" such as genomics, proteomics and metabolomics, research in the field of herbal psychopharmacology has gained momentum, providing a faster and informative platform for thorough evaluation of herbal drugs and formulations. In this article, we have reviewed several medicinal plants and their formulations that have shown potential anxiolytic and anti-depressant activities and have been screened for their biological mechanisms either at the gene, protein or metabolic level.
Topics: Animals; Anti-Anxiety Agents; Anxiety; Herbal Medicine; Humans; Mood Disorders; Pharmacogenetics; Plant Extracts; Plants, Medicinal
PubMed: 30551365
DOI: 10.1016/j.biopha.2018.10.135