Anxiolytic Drugs Research Articles

The effect of magnesium sulfate on memory and anxiety-like behavior in a rat model: an investigation of its neuronal molecular mechanisms

ABSTRACT Background Anxiety is an adaptive response to potentially threatening conditions. Excessive and uncontrolled anxiety responses become nonadaptive and cause anxiety disorders. To better understand the anxiety-modulating effects of Mg sulfate, behavioral test batteries in the assessment of anxiety and learning and memory functions were performed simultaneously over a time period. This study also examines the effects of Mg sulfate compared to diazepam, an anxiolytic drug with amnestic effects on anxiety-like behavior, as well as possible oxidative-nitrosative stress and hippocampal changes in male rats exposed to predator odor. Methods Young adult Sprague-Dawley male rats were used. The rats were assessed using a comprehensive neurobehavioral test battery consisting of novel object recognition, open field, and successive alleys tasks. Anxiety was induced by cat odor, and diazepam and Mg were used as study drugs. Of the frontal cortex and hippocampus, the state of total oxidant and antioxidant and NO levels and histological examination of hippocampal CA1, CA2, CA3, and DG regions were performed. Results Diazepam- and Mg-treated rats showed an improvement in anxiety-related behavior to predator odors. Furthermore, Mg treatment alleviated some of the increasing oxidative stress in the frontal cortex and hippocampus of rats, while diazepam treatment in particular enhanced hippocampal oxidant and antioxidant activity. In addition, brain NO increase induced by animal odor exposure or diazepam treatment was ameliorated by Mg administration. Conclusions Overall, our work suggests that Mg had a partial anxiolytic effect on anxiety-like behaviors, although not as much as diazepam, and this effect varied depending on the dose. Mg treatment might counteract increased oxidative stress and elevated NO levels in the brain.

Review on Role of Yoga in Chittodvega w.s.r. to Generalized Anxiety Disorder

Mental health disorders are mentioned as 3rd health burden in India according to WHO survey. Generalized anxiety disorders are a chronic anxiety disorder characterized by excessive and uncontrollable worry and anxiety about everyday life events and situations. In Ayurveda many psychological disorders are mentioned in Samhitas. Terms like Asvastha Chitta, Chittavimbhramsa, Chittodvega etc. seems similar to Generalized anxiety disorder, however Chittodvega seems to be nearest correlation for this disease entity. Acharya Charaka has listed Chittodvega as Manas Dosha Vikara. People with symptoms of Generalized anxiety disorder always tend to expect failure and can't stop worrying, Clinical trials have shown that anxiolytic drugs alone have limited long-term efficacy. Moreover, they often have adverse side effects including dependency, drowsiness, impaired cognition and memory and sexual dysfunction. Being an alarming disease GAD needs an effective management. Nowadays Yoga is considered as a popular approach to improve emotional health. Yoga, a form of holistic mind–body medicine, that includes the use of physical postures (Asanas), breathing practices (Pranayamas), meditations, relaxation techniques and lifestyle changes based on ancient yogic philosophy. Pranayama should be practiced to remove the blockages and to lift you out of the Tamasik and Rajasik states. Asanas empathizes physical strength and helps to maintain balance between mind and body. Yoga helps to restraint unnecessary mental fluctuations and thus helps in stabilizing and calming the mind. Thus it might be an effective and safe intervention for individuals with GAD.

A Review on Chittodvega w.s.r to Generalized Anxiety Disorder and its Management

With the advent of modern science, human life has become much faster and more stressful. Psychiatric disorders are therefore expanding today, A wide range of psychiatric conditions have been described in Ayurveda. Ayurveda follows psychosomatic approach of health. Chittodvega is a Manasavikara mentioned by Charaka which is considered as a perfect word for highlighting the status of anxiety, Generalized Anxiety Disorder. Chittodvega can exists as a separate disease or can be an etiological factor for other psychic and psychosomatic diseases. Generalized anxiety disorder (GAD) is a mental health disorder that produces fear worry and a constant feeling of being overwhelmed. This on-going worry and tension may be accompanied by physical symptoms, such as restlessness, feeling on edge or easily fatigued, difficulty concentrating, muscle tension or problems sleeping. Being an alarming disease, it requires effective management. In recent years several synthetic drugs have been introduced for the treatment of anxiety disorders. Clinical trials have shown that anxiolytic drugs alone have limited long term efficacy and one cannot avoid major side effects such as drug dependence, drug resistance, sedation etc. Ayurveda follows psychosomatic approach of health. Acharya Charaka explains three types of therapies of physical and mental disorders Daivavyapasraya, Yuktivyapasrya, Satvajaya Chikitsa. So the present study deals with systemic review of Chittodvega from all the classics of Ayurveda and its management.

Insights into the binding of buspirone to human serum albumin using multi-spectroscopic and molecular docking techniques

Buspirone is an anxiolytic drug that plays a significant role in managing anxiety disorders and alleviating their symptoms as well. Several techniques were utilized to study the interaction between buspirone and human serum albumin under physiological conditions, including UV–vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism, Fourier transform infrared spectroscopy (FT-IR), equilibrium dialysis, and molecular docking. The results of this study demonstrated that buspirone quenched the intrinsic fluorescence of human serum albumin through a mixed mechanism. Moreover, the binding constants (Kb), the quenching constants (Ksv), and thermodynamic parameters were calculated at various temperatures. The binding process of buspirone to human serum albumin showed a cooperative binding pattern, confirmed by the Scatchard diagram and Hill coefficient. Molecular docking results showed that buspirone interacted with the IIA, IIIA, and IIB subdomains of human serum albumin and slightly changed its conformation. It was also found that hydrophobic forces played a major role in this interaction. This study consequently proves that BSH as a drug can be transported by blood albumin. Additionally, due to its ratiometric response in absorbance upon binding to a biological target, HSA can be used as a molecular probe to follow biomolecular interactions.

Patient Anxiety in Endoscopy: A Comparative Analysis of Single vs. Dual Procedure Effects.

This study aimed to investigate the difference in anxiety levels between patients undergoing gastroscopy only and those subjected to both gastroscopy and colonoscopy. Despite known preoperative anxiety impacts, no prior research has compared these specific patient groups. A total of 150 patients were divided equally into two groups: Group I, undergoing gastroscopy only, and Group II, undergoing gastroscopy and colonoscopy. Inclusion criteria were patients in the age range 18-70 years and having an ASA (American Society of Anesthesiologists) physical status classification of I-III. Exclusion criteria were patients outside the age range, and patients with hearing disorders, psychiatric disorders, dementia, or recent anxiolytic drug use. Anxiety was analysed using the Beck Anxiety Inventory Scale before procedures, without any premedication. Patients in Group II had significantly higher anxiety levels, with particular increases noted in symptoms such as leg weakness and tremors, inability to relax, and fears of adverse events and death. These results highlighted a considerable elevation in anxiety among patients anticipating or undergoing combined endoscopic procedures. The findings revealed that undergoing combined gastroscopy and colonoscopy procedures significantly elevated patient anxiety levels compared to gastroscopy alone. This suggests a critical need for healthcare providers to implement more strong preoperative counselling and anxiety reduction strategies for patients facing multiple procedures. Addressing this increased anxiety could lead to better patient experiences, reduced procedural complications, and improved satisfaction and outcomes.

Effect of Benzodiazepines and Z-Drug Medications during Antenatal and Postnatal Depression and Anxiety: A Systematic Review and Meta-Analysis.

Benzodiazepines (BZD) and Z-drugs are often prescribed for alleviating such symptoms and treating maternal psychiatric disorders and epilepsy. However, their use is limited due to the apprehensions and risks related to poor maternal and neonatal outcomes. This meta-analysis evaluated the rationality and efficacy of using Benzodiazepines and Z-drugs for managing anxiety and depression in pregnant women. The meta-analysis was based on a systematic review through keyword search utilizing Scopus, Pubmed, and Cochrane databases. One hundred three articles were deemed eligible, but only 21 articles were selected for the meta-analysis. The meta-analysis showed that despite the indication for anxiety and depression in pregnant women, the usage of BZD and Z-drugs was significantly low compared to other psychotropic medications, with no therapy or non-pharmacological interventions. Our study shows that, during the antenatal and postnatal period, women required more anti-depressants, anti-psychotics, and anxiolytic drugs. Although BZDs and Z-drugs are effective in managing insomnia during peripartum and post-partum, they are either ineffective or contraindicated for managing anxiety and depression in pregnant women compared to anxiolytics and anti-depressants.

Targeting N-Methyl-d-Aspartate Receptors in Neurodegenerative Diseases.

N-methyl-d-aspartate receptors (NMDARs) are the main class of ionotropic receptors for the excitatory neurotransmitter glutamate. They play a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of several subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, and excitotoxicity. The present review will detail the structure, composition, and localization of NMDARs, their role and regulation at the glutamatergic synapse, and their impact on cognitive processes and in neurodegenerative diseases (Alzheimer's, Huntington's, and Parkinson's disease). The pharmacology of different NMDAR antagonists and their therapeutic potentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising development as a neuroprotective agent in Alzheimer's disease, in complement to its reported efficacy as a tomography radiotracer for NMDARs and an anxiolytic drug in post-traumatic stress disorder.

Evolution of the profiles of new psychotropic drug users before and during the COVID-19 crisis: an original longitudinal approach through multichannel sequence analysis using the French health-care database.

The COVID-19 pandemic has had a substantial impact on mental health. An increase in the use of anxiolytic, hypnotic, and antidepressant drugs has been highlighted in France, but with no information at the individual level (trajectories) or concerning patient characteristics. The objective of this study was to describe the profile of new psychotropic drug users since the beginning of the pandemic. We formed two historical cohorts using the Pays-de-la-Loire regional component of the National Health Data System (SNDS): a "COVID-19 crisis cohort" (2020-2021) and a "control cohort" (2018-2019). We analyzed reimbursements for psychotropic medications (anxiolytics, antidepressants, hypnotics, mood stabilizers, and antipsychotics) using a multichannel sequence analysis and performed clustering analysis of sequences. The proportion of new consumers of psychotropic drugs was higher in the COVID-19 crisis cohort (18.0%) than that in the control cohort (16.0%). In the COVID-19 cohort, three clusters of psychotropic drug users were identified, whereas four clusters were identified in the control cohort. A time lag in treatment initiation was observed in the COVID-19 crisis cohort (September) compared with the control cohort (July). This study is one of the first to analyze the profile of psychotropic treatment users during the COVID-19 crisis. Our analysis sheds light on changes in patterns of psychotropic drug use during the COVID-19 pandemic, possibly associated with changes in prescribing conditions and mental health conditions during the crisis. This study also provides an example of the application of an innovative longitudinal analysis methodology in the field of pharmacoepidemiology.

Rodent tests of depression and anxiety: Construct validity and translational relevance

Behavioral testing constitutes the primary method to measure the emotional states of nonhuman animals in preclinical research. Emerging as the characteristic tool of the behaviorist school of psychology, behavioral testing of animals, particularly rodents, is employed to understand the complex cognitive and affective symptoms of neuropsychiatric disorders. Following the symptom-based diagnosis model of the DSM, rodent models and tests of depression and anxiety focus on behavioral patterns that resemble the superficial symptoms of these disorders. While these practices provided researchers with a platform to screen novel antidepressant and anxiolytic drug candidates, their construct validity—involving relevant underlying mechanisms—has been questioned. In this review, we present the laboratory procedures used to assess depressive- and anxiety-like behaviors in rats and mice. These include constructs that rely on stress-triggered responses, such as behavioral despair, and those that emerge with nonaversive training, such as cognitive bias. We describe the specific behavioral tests that are used to assess these constructs and discuss the criticisms on their theoretical background. We review specific concerns about the construct validity and translational relevance of individual behavioral tests, outline the limitations of the traditional, symptom-based interpretation, and introduce novel, ethologically relevant frameworks that emphasize simple behavioral patterns. Finally, we explore behavioral monitoring and morphological analysis methods that can be integrated into behavioral testing and discuss how they can enhance the construct validity of these tests.

The open field assay is influenced by room temperature and by drugs that affect core body temperature.

The open field assay is used to study anxiety-related traits and anxiolytic drugs in rodents. This assay entails measuring locomotor activity and time spent in the center of a chamber that is maintained at ambient room temperature. However, the ambient temperature in most laboratories varies daily and seasonally and can differ between buildings. We sought to evaluate how varying ambient temperature and core body temperature (CBT) affected open field locomotor activity and center time of male wild-type (WT, C57BL/6) and Transient Receptor Potential Subfamily M Member 8 ( Trpm8) knock-out ( Trpm8 -/- ) mice. TRPM8 is an ion channel that detects cool temperatures and is activated by icilin. Mice were placed in the open field at 4°C and 23°C for 1 hour. Distance traveled and time spent in the center were measured. Mice were injected with icilin, M8-B, diazepam, or saline, and changes in activity level were recorded. The cooling agent icilin increased CBT and profoundly reduced distance traveled and center time of WT mice relative to controls. Likewise, cooling the ambient temperature to 4°C reduced distance traveled and center time of WT mice relative to Trpm8 -/- mice. Conversely, the TRPM8 antagonist (M8-B) reduced CBT and increased distance traveled and center time of WT mice when tested at 4°C. The TRPM8 antagonist (M8-B) had no effect on CBT or open field behavior of Trpm8 -/- mice. The anxiolytic diazepam reduced CBT in WT and Trpm8 -/- mice. When tested at 4°C, diazepam increased distance traveled and center time in WT mice but did not alter open field behavior of Trpm8 -/- mice. Environmental temperature and drugs that affect CBT can influence locomotor behavior and center time in the open field assay, highlighting temperature (ambient and core) as sources of environmental and physiologic variability in this commonly used behavioral assay.

Comparison of perception of stress and consumption of anxiolytics in hospital and out-hospital conditions: a cross-sectional study.

The workplace is a place where medical workers are exposed to extreme stress, particularly during medical emergencies or events of epidemic or pandemic proportions. Anxiolytic therapy is often used to overcome professional challenges. Deepening knowledge about the prevalence of the use of anxiolytics and the perception of stress among medical workers enables the timely recognition of problems and the preparation of measures to improve the working conditions and quality of life of medical workers. The study's primary objective was to investigate whether there were differences in the usage of anxiolytics among healthcare professionals in and out of the hospital. In addition to the main objective, there are other objectives that have been established: To examine whether there are statistically justified differences in stress perceptions between hospital and outpatient healthcare professionals; 2. To examine the stress factors in the workplace in both hospital and outpatient settings. To compare the frequency of taking anxiolytics with respect to various variables (age, seniority, occupation and level of education); 4. determines the impact of working conditions on stress perception and life satisfaction in healthcare professionals. The design of research: Cross-sectional research. The research involved 159 healthcare professionals in Slavonski Brod: 96 employees of the General Hospital "Dr. Josip Benčević" and 63 employees of the Health Center and the Institute for Emergency Medicine of Brodsko-Posavina County. Respondents were able to participate in the study by filling out questionnaires online. The questionnaire was designed to be voluntary and anonymous and contained 53 questions. Statistically significant differences were shown in the perception of stress, which is greater in hospital staff, than in the difference between stressors in the workplace, where hospital staff showed higher values in all categories, but three factors are more significant differences: "Organization of the workplace and financial issues," "Conflicts and communication at work" and "Professional and intellectual requirements." There are significant differences in the frequency of using anxiolytics with the assistance of a psychiatrist. Working conditions have a much greater impact on the perception of stress and life satisfaction in hospital staff, while in hospital staff only a weak link between the perception of stress and life satisfaction is expressed. Anxiolytics are consumed by 27.10% of hospital workers and 23.80% of outside-the-hospital workers. The consumption of anxiolytic drugs by healthcare professionals in hospital and outpatient conditions does not make a significant difference, but they do have statistically significant differences in their perception of stress.

Anaesthetic-sparing effect of the anxiolytic drug tasipimidine in Beagle dogs

ObjectiveTo evaluate the effect of oral tasipimidine on dog handling, ease of catheter placement and propofol and isoflurane requirements for anaesthesia. Study designPlacebo-controlled, randomized, blinded, experimental trial. AnimalsA group of seven adult Beagle dogs weighing (mean ± standard deviation) 13.1 ± 2.7 kg with a mean age of 18.6 ± 1 months. MethodsThe dogs underwent four treatments before induction of anaesthesia with propofol. PP: placebo orally (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) intravenously (IV). TP: tasipimidine 30 μg kg–1 (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) IV. TMP: tasipimidine 30 μg kg–1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg–1 IV. TMPD: tasipimidine 30 μg kg–1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg–1 and dexmedetomidine 1 μg kg–1 IV followed by a dexmedetomidine constant rate infusion of 1 μg kg–1 hour–1.Sedation, response to catheter placement, intubation quality, time to loss of consciousness, time to intubation, required dose of propofol and minimum alveolar isoflurane concentration preventing motor movement (MACNM) were determined.A mixed-model analysis or the Friedman and Mann–Whitney test were used; p-value < 0.05. ResultsResponse to catheter placement did not differ between treatments. Tasipimidine alone reduced the propofol dose by 30%. Addition of methadone or methadone and dexmedetomidine reduced the propofol dose by 48% and 50%, respectively. Isoflurane MACNM was reduced by 19% in tasipimidine-medicated dogs, whereas in combination with methadone or methadone and dexmedetomidine, isoflurane MACNM was reduced by 35%. Conclusions and clinical relevanceAn anxiolytic dose of tasipimidine induced mild signs of sedation in dogs and reduced propofol and isoflurane requirements to induce and maintain anaesthesia, which needs to be considered in an anaesthetic plan.

A Comparison of the Anxiolytic Properties of Tofisopam and Diazepam: A Double-Blind, Randomized, Crossover, Placebo-Controlled Pilot Study.

New clinical reports have recently been published on tofisopam-an anxiolytic drug currently registered as a benzodiazepine-after a long break in this research area. Neurobiological studies concerning its properties, which differ from those of benzodiazepines, are underway. The analyses presented in this study aimed to compare the effects of tofisopam, diazepam, and a placebo in the treatment of anxiety symptoms. A total of 66 outpatients (43 women and 23 men) with generalized anxiety disorder aged 19 to 74 years (M = 41.4; SD = 13.2) were randomized in three groups receiving (1) tofisopam (50 mg three times a day), (2) diazepam (5 mg three times a day), or (3) a placebo for 2 weeks. Then, throughout a 2-week washout period, the patients were monitored for withdrawal symptoms. During the last 2 weeks, the effects of tofisopam (50 mg three times a day) and diazepam (5 mg three times a day) were compared (crossover design). The mean improvement on the Hamilton Anxiety Rating Scale was significantly higher in both the tofisopam and diazepam groups compared to the placebo group. There were no significant differences between the effects of diazepam and tofisopam, whereas adverse effects and withdrawal symptoms occurred less frequently in the tofisopam group. Tofisopam did not impair cognitive abilities, and related withdrawal symptoms resembled those of the placebo. If larger future studies corroborate these findings, tofisopam should be classified as a homophtalazine.

Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drug

Previously at the Zakusov Research Institute of Pharmacology the first dipeptide ligand TSPO, the compound N-phenylpropionyl-L-tryptophanyl-L-leucine amide (laboratory code GD-102), was designed and synthesized. The anxiolytic activity was detected for this compound at the doses 0.01–1.0 mg/kg intraperitoneally (ip) in mice. Dipeptide GD-102 also possessed antidepressant-like activity at the doses 0.01 and 0.05 mg/kg ip in BALB/c mice in the Porsolt forced swim test. The ligand properties of dipeptide GD-102 to TSPO were confirmed by pharmacological inhibitory analysis and molecular docking. This work is devoted to the development of the optimal scheme for the synthesis of the GD-102. 3 methods were tried — 1 activated succinimide esters method, 2 activated pentafluorophenyl ethers method and 3 imidazolide method. These three synthesis schemes have been compared in terms of yield and optical purity of the final product. It was shown that the optimal synthesis scheme is the first one, using succinimide esters.

Benzodiazepine derivatives for the treatment of neuropharmacological disorders and pain management: Docking investigations and in-vivo studies

Benzodiazepines are well-known for their medicinal properties. The current study aimed to evaluate and seek new therapeutic possibilities of some of these compounds for addressing anxiety and pain. Four benzodiazepine derivatives were synthesized, characterized, and subjected to computational assessment of the GABAergic response upon interaction with human GABA-A receptors (PDBID: 6×3x) relative to the drug diazepam (DZP) to achieve the objective. Apart from the docking analysis, ADME analysis of the compounds was also performed. Following the in-silico evaluations, two of the synthesized compounds (designated as P3 and P4) were identified for subsequent in-vivo investigations utilizing laboratory rats to explore their anxiolytic potential in comparison to diazepam, and their analgesic efficacy relative to diclofenac sodium. The combination of in-silico and in-vivo assessments uncovered the binding sites of P4 (a fluoro derivative) and its potential as a superior anxiolytic drug compared to P3 (a hydroxy derivative) for analgesic relief. The ADME pharmacokinetic evaluation of the synthesized compounds by Lipinski rule of 5 suggested the oral bioavailability of these drugs. These findings are important as they provide valuable insights into the potential development of new anxiolytic and analgesic agents from the benzodiazepine derivatives that can be easily synthesized and developed into affordable drugs.

Differential effects of intra-RMTg infusions of pilocarpine or 4-DAMP on regulating depression- and anxiety-like behaviors

Depression and anxiety are associated with dysfunction of the mesolimbic dopamine system. The rostromedial tegmental nucleus (RMTg) is predominantly composed of GABAergic neurons that exhibit dense projections and strongly inhibit mesolimbic dopaminergic neurons, proposed as a major “brake” for the system. Consequently, the RMTg may be a crucial brain region for regulating these emotions. The central cholinergic system, particularly the muscarinic receptors, plays an important regulatory role in depression and anxiety. M3 muscarinic receptors are distributed on GABAergic neurons in the RMTg, but their involvement in the regulation of depression and anxiety remains uncertain. This study aimed to examine the effects of RMTg M3 muscarinic receptors on regulating depression- and anxiety-like behaviors in adult male Wistar rats, as assessed through the forced swim, tail suspension, and elevated plus maze tests. The results showed that intra-RMTg injections of the M1/M3 muscarinic receptors agonist, pilocarpine (3, 10, and 30 μg/side), or the M3 muscarinic receptors antagonist, 4-DAMP (0.5, 1, and 2 μg/side), did not alter the immobility time in the forced swim and tail suspension tests. Additionally, pilocarpine (30 μg/side) decreased time spent in open arms and increased time in closed arms in the elevated plus maze; while 4-DAMP (1 and 2 μg/side) played the opposite role by increasing time spent in open arms and decreasing time in closed arms. These findings suggest that RMTg M3 muscarinic receptors have differential effects on regulating depression- and anxiety-like behaviors. Enhancing or inhibiting these receptors can produce anxiogenic or anxiolytic effects, but have no impact on depression-like behavior. Therefore, RMTg M3 muscarinic receptors are involved in regulating anxiety and may be a potential therapeutic target for anxiolytic drugs.

The use of anxiolytic drugs for the correction of behavioral disorders in mammals

The issue of stress and behavioral disorders are growing significantly in the contemporary word in humans and animals alike. Various drugs are used to modify affected behavior, including psychotropic, anticonvulsant, antihistamines, hormones, analgesics, and neuroleptics. Psychotropic drugs are prescribed for animals with behavioral disorders, signs of anxiety or hypersensitivity. Improving the methods of diagnosing and treating behavioral disorders in animals can enhance animal welfare and optimize animal husbandry technology. Future research should be aimed at improving and optimizing the use of psychotropic drugs for behavioral disorders of various animal species. The main indication for the use of anxiolytic drugs is behavioral disorders associated with anxiety in wild and domestic animals. When anxiolytic drugs are used in mammals their pharmacological properties, the dependence of their action on the route of administration, age and species of the animal, and the ability to selectively affect the central nervous system should be taken into account. The most commonly used drugs for the treatment of behavioral disorders in animals are fluoxetine, amitriptyline, escitalopram, haloperidol, zuclopentixol and azaperone. Fluoxetine is an effective drug for the treatment of dogs with behavioral disorders associated with psychological changes. An important component of escitalopram's pharmacological effect is the psychomotor influence, when the animal's behavior changes are due to improved motor activity. Zuclopentixol has a wide range of anxiolytic, sedative and analgesic effects when used in wild cloven-hoofed animals. Amitriptyline along with antidepressant properties, has a local analgesic impact. Azaperone has a pronounced anxiolytic and sedative effect on animals. It is widely used as an anti-stress agent to overcome anxiety caused by weaning, regrouping or veterinary manipulations. Azaperone is often used to control aggressive behavior in group housing, especially in the pig industry. The psychotropic drugs surveyed in this paper, along with direct anxiolytic action, are able to manifest additional physiological effects, which should be taken into account when developing treatment protocols for animals with behavioral problems. Further targeted studies are required to assess the pharmacological effects of anxiolytic drugs in animals.

Use of Antidepressant and Anxiolytic Drugs in Scandinavian Countries between 2006 and 2021: A Prescription Database Study

Introduction. The use of antidepressant and anxiolytic drugs has changed in Scandinavian countries over recent decades, with notable national variations. Objective. To describe and compare antidepressant and anxiolytic drug use in Norway, Sweden, and Denmark. Methods. Data included each country’s prescription registers from 2006 to 2021. The measures were period (1-year) prevalence (users per 1000 inhabitants) and therapeutic intensity (TI; daily defined dose (DDD) per 1000 inhabitants per day), overall, by drug classes and age groups. Results. The prevalence of antidepressant use increased from 2006 to 2021 and was highest in Sweden (78 to 107 users per 1000 inhabitants) and lowest in Norway (61 to 69 users per 1000 inhabitants). The prevalence of anxiolytic use decreased, most steeply in Denmark (50 to 18 users per 1000 inhabitants). The TI of antidepressants increased consistently in Norway and Sweden, but more variably in Denmark. Sweden had the highest increase in TI of antidepressants (56%). The TI of anxiolytics declined most markedly in Denmark (by 75%). The prevalence of antidepressant and anxiolytic use was highest among adults ≥65 years. The prevalence of antidepressant use increased across age groups in Sweden and young people (5-19 years) in Norway, but not in Denmark. Conclusions. The use of antidepressants increased in Scandinavia in 2006-2021, but decreased for anxiolytics, with country variations in the number of users and the amount used. Future research should target factors underlying high antidepressant and anxiolytic use in older adults across countries and increasing antidepressant use in Sweden and among young Norwegians.

Effect of Agaricus blazei Murill on exploratory behavior of mice-model.

Increased anxiety and depressive symptoms have reported to be its association with long term illness. Because of having unwanted effects of newly available drugs, patients administering anxiolytic drugs usually discontinue the treatment before they are completely recovered. Therefore, there is a serious need to develop new anxiolytic drugs. The anxiolytic effect of hydro-alcoholic extract of Agaricus blazei in animal models was assessed. 24 male mice (Mus musculus genus) were included in the study. Four groups were prepared and each group contained six animals. The groups were vehicle control, positive control (diazepam 1.0 mg/kg, i.p.) as well as two treatment groups receiving Agaricus blazei hydro-alcoholic extract at a dose of 136.50 mg/kg and 273.0 mg/kg orally. The Marble burying test, Nestlet shredding test and Light and Dark box test used to assess anxiolytic activity. Mice administered with diazepam 1.0 mg/kg, i.p. while hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) was administered via oral route which exhibited marked reduction in number of marbles-burying as compared to vehicle control group. Mice administered with diazepam 1.0 mg/kg, i.p. and Oral administration of hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) exhibited significant decrease in nestlet shredding in comparison to vehicle control group. The oral administration of hydro-alcoholic extract at a dose of 136.5mg/kg and 273mg/kg showed elevation in time spent in light box and was comparable to standard treated group while time spent by mice following oral administration of hydro-alcoholic extract of Agaricus blazei at a dose of 273.0 mg/kg also showed elevation and was found to be more near to standard treated group (diazepam 1 mg/kg, i.p.).

Patterns of Antidepressant and Anxiolytic Use and Spending in 14 European Countries (2012-2021): A Comprehensive Time Series Analysis.

The assessment of antidepressant and anxiolytic consumption and expenditures represents a reliable barometer of the burden of such mental health disorders and the effectiveness of relative healthcare services. The current analysis aims to evaluate trajectories of consumption and expenditures of antidepressant and anxiolytic drugs to define patterns of usage and spending across 14 European countries between 2012 and 2021. A retrospective longitudinal study was performed based on pooled time series secondary data analysis over 2012/2021. Defined Daily Doses (DDD) per 1000 inhabitants and health expenditure per capita were analysed. Linear and quadratic trends were computed to determine relationships between the variables of interest. Only 2 patterns of consumption/expenditure of antidepressants can be identified: consumption and expenditure both grow; consumption grows, and spending decreases. Consumption and expenditures registered 2 main patterns, decreasing in most European countries and increasing only in 2 cases. Prevailing patterns of consumption and spending show an increase in antidepressants and a decrease in anxiolytics. The variation in consumption of such drugs during this timeframe is attributable to several reasons, such as the epidemiological characteristics of mental disease, for instance, the prevalence and incidence of disorders, the accessibility of drugs and alternative treatments, like psychotherapy, different clinical practices and national guidelines. However, such analyses deserve attention for targeted policies and strategies for promoting mental health.