CDNF Exerts Anxiolytic, Antidepressant-like, and Procognitive Effects and Modulates Serotonin Turnover and Neuroplasticity-Related Genes.

Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor because it does not bind to a known specific receptor on the plasma membrane and functions primarily as an unfolded protein response (UPR) regulator in the endoplasmic reticulum. Data on the effects of CDNF on nonmotor behavior and monoamine metabolism are limited. Here, we performed the intracerebroventricular injection of a recombinant CDNF protein at doses of 3, 10, and 30 µg in C57BL/6 mice. No adverse effects of the CDNF injection on feed and water consumption or locomotor activity were observed for 3 days afterwards. Decreases in body weight and sleep duration were transient. CDNF-treated animals demonstrated improved performance on the operant learning task and a substantial decrease in anxiety and behavioral despair. CDNF in all the doses enhanced serotonin (5-HT) turnover in the murine frontal cortex, hippocampus, and midbrain. This alteration was accompanied by changes in the mRNA levels of the 5-HT1A and 5-HT7 receptors and in monoamine oxidase A mRNA and protein levels. We found that CDNF dramatically increased c-Fos mRNA levels in all investigated brain areas but elevated the phosphorylated-c-Fos level only in the midbrain. Similarly, enhanced CREB phosphorylation was found in the midbrain in experimental animals. Additionally, the upregulation of a spliced transcript of XBP1 (UPR regulator) was detected in the midbrain and frontal cortex. Thus, we can hypothesize that exogenous CDNF modulates the UPR pathway and overall neuronal activation and enhances 5-HT turnover, thereby affecting learning and emotion-related behavior.

Chronic pregabalin treatment reduced anxiety, and acute pregabalin treatment increased depression-like behaviors in rats.

BACKGROUND: Pregabalin is an antiepileptic drug that binds to the alpha-2/delta unit at presynaptic voltage-dependent calcium channels. We aimed to investigate the effect of acute and chronic pregabalin administration on anxiety and depression-like behaviors. METHODS: Fifty-six male Wistar albino rats were divided into seven groups: control, vehicle, and five different dose groups (5, 10, 30, 60, and 100 mg/kg). Pregabalin was administered for two weeks. Depression-like behaviors were evaluated by Forced swimming test. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT), Elevated Plus Maze (EPM), and light-dark box. Subjects underwent the forced swimming test (FST) after the first dose, while the open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB) were performed after two weeks of treatment. Further sucrose preference test was conducted to evaluate anhedonia until the end of the experiment. RESULTS: In the forced swimming test, depression-like behaviors increased after acute single-dose administration of 10, 30, 60, 100 mg/kg pregabalin. According to OFT results, chronic 100 mg/kg pregabalin showed anxiolytic effects by decreasing grooming, and freezing behaviors. In addition, 100 mg/kg chronic pregabalin administration significantly increased the time spent in the central region, the number of entries to the center, and the unsupported rearing number without causing any change in locomotor activity. According to EPM results, both chronic 60 and 100 mg/kg pregabalin treatments showed anxiolytic effects by increasing open arm time and head dipping behavior. In addition, 60 and 100 mg/kg chronic pregabalin administration significantly decreased stretch attend posture. All pregabalin administrations between 5 and 100 mg/kg displayed anxiolytic effects in the LDB. Sucrose preference was above 65% for the duration of all experiments and subjects did not show anhedonia. CONCLUSION: Acute pregabalin treatment triggered depression-like behaviors. Anhedonia, which may be associated with depression, was not observed during chronic treatment. Moreover, chronic treatment with pregabalin revealed potent anxiolytic effects in different behavior patterns and doses for all tests of unconditional anxiety. In particular, 100 mg/kg chronic pregabalin administration decreased anxiety-like behaviors in all experiment setups. Although the anxiolytic effect was demonstrated in chronic treatment, acute treatment of pregabalin induced depression-like behaviors, and thus in clinical practice should be done with caution, especially in patients with anxiety-depression comorbidity.

[Pharmacological effects of fonturacetam (Actitropil) and prospects for its clinical use]. / Farmakologicheskie effekty fonturatsetama (Aktitropil) i perspektivy ego klinicheskogo primeneniya.

Phenylpiracetam (PP) is a nootropic drug with additional pharmacological effects, including anxiolytic, antiasthenic, antidepressant, anti-inflammatory and anticonvulsant effects. The paper presents the results of an analysis of experimental and clinical studies, which indicate the prospects for the use of PP in cerebral ischemia, neurodegenerative pathologies, epilepsy, asthenia, and mental disorders. The adaptogenic properties and mitochondrial protective effect of PP are considered, assessments of the possible effect of PP on neurotransmitter systems, regulation of carbohydrate and fat metabolism with the prospects for the use of PP in patients with metabolic syndrome.

Network pharmacology screening, in vitro and in vivo evaluation of antianxiety and antidepressant drug-food analogue.

BACKGROUND: Depression and anxiety disorders are prevalent psychiatric conditions, and currently utilized chemical drugs typically come with significant adverse effects. China boasts a wealth of medicinal and food herbs known for their safe and effective properties. PURPOSE: This study aimed to develop novel formulations with improved antidepressant and anxiolytic effects derived from medicinal and food herbs. STUDY DESIGN: Screening combinations with antidepressant and anxiolytic effects using techniques such as network pharmacology and validating their effects in vitro and in vivo experiments. METHODS: Utilizing network pharmacology and molecular docking, we identified the top ten medicinal herbs with anxiolytic and antidepressant potential. Herbs with cytoprotective effects and non-toxic characteristics were further screened to formulate the herbal blends. Subsequently, we established a PC12 cell injury model and a chronic unpredictable mild stress (CUMS) model in mice to assess the effects of our formulations. RESULTS: Ten medicinal herbs were initially screened, and six of them were deemed suitable for formulating the blend, namely Gancao, Dazao, Gouqizi, Sangye, Huangqi, and Jinyinhua (GDGSHJ). The GDGSHJ formulation reduced Lactate Dehydrogenase (LDH) leakage, decreased apoptosis, and demonstrated a favorable antidepressant and antianxiety effect in the CUMS mouse model. Besides, GDGSHJ led to the upregulation of serum 5-Hydroxytryptamine (5-HT) content and brain tissue 5-HT, Gamma-aminobutyric acid (GABA), and Dopamine (DA) levels. It also downregulated the expression of SLC6A4 and SLC6A3 genes in the mouse hippocampus while upregulating HTR1A, DRD1, DRD2, and GABRA1 genes. CONCLUSION: Our formulation exhibited robust antidepressant and antianxiety effects without inducing substantial toxicity. This efficacy appears to be mediated by the expression of relevant genes within the hippocampus of mice. The formulation achieved this effect by balancing 5-HT levels in the serum and DA, GABA, and 5-HT levels within brain tissue.

Psychotropic drug prescribing before and during the COVID-19 pandemic among people with depressive and anxiety disorders: a multinational network study.

BACKGROUND: People with mental health conditions were potentially more vulnerable than others to the neuropsychiatric effects of the COVID-19 pandemic and the global efforts taken to contain it. The aim of this multinational study was to examine the changes in psychotropic drug prescribing during the pandemic among people with depressive and anxiety disorders. METHODS: This study included electronic medical records and claims data from nine databases in six countries (France, Germany, Italy, the UK, South Korea, and the USA) of patients with a diagnosis of depressive or anxiety disorders between 2016 and 2021. The outcomes were monthly prevalence rates of antidepressant, antipsychotic, and anxiolytic drug prescribing. The associations between the pandemic and psychotropic drug prescribing were examined with interrupted time series analyses for the total sample and stratified by sex and age group. People with lived experience were not involved in the research and writing process. FINDINGS: Between Jan 1, 2016 and Dec 31, 2020, an average of 16 567 914 patients with depressive disorders (10 820 956 females [65·31%] and 5 746 958 males [34·69%]) and 15 988 451 patients with anxiety disorders (10 688 788 females [66·85%] and 5 299 663 males [33·15%]) were identified annually. Most patients with depressive disorders and anxiety disorders were aged 45-64 years. Ethnicity data were not available. Two distinct trends in prescribing rates were identified. The first pattern shows an initial surge at the start of the pandemic (eg, antipsychotics among patients with depressive disorders in MDCD_US (rate ratio [RR] 1·077, 95% CI 1·055-1·100), followed by a gradual decline towards the counterfactual level (RR 0·990, 95% CI 0·988-0·992). The second pattern, observed in four databases for anxiolytics among patients with depressive disorders and two for antipsychotics among patients with anxiety disorders, shows an immediate increase (eg, antipsychotics among patients with anxiety disorders in IQVIA_UK: RR 1·467, 95% CI 1·282-1·675) without a subsequent change in slope (RR 0·985, 95% CI 0·969-1·003). In MDCD_US and IQVIA_US, the anxiolytic prescribing rate continued to increase among patients younger than 25 years for both disorders. INTERPRETATION: The study reveals persistently elevated rates of psychotropic drug prescriptions beyond the initial phase of the pandemic. These findings underscore the importance of enhanced mental health support and emphasise the need for regular review of psychotropic drug use among this patient group in the post-pandemic era. FUNDING: University Grants Committee, Research Grants Council, The Government of the Hong Kong Special Administrative Region.

Anxiolytic Action of Dipeptide Mimetic of the BDNF Loop 2 in Adult Animals.

We studied the anti-anxiety effect of a low-molecular-weight mimetic of the BDNF loop 2, hexamethylenediamide bis-(-N-hexanoyl-L-seryl-L-lysine) (GTS-201) in adult animals. GTS-201 at a dose of 5 mg/kg after acute intraperitoneal administration to outbred male and female rats increased the time spent in the open arms and the number of entries into the open arms in the elevated plus maze (EPM). In "highly emotional" male BALB/c mice, GTS-201 exhibited a dose-dependent anxiolytic effect in the EPM in a dose range of 0.5-2.0 mg/kg with a maximum effective dose of 1 mg/kg. These data confirm the previously revealed anti-anxiety properties of GTS-201 in inbred male and female BALB/c mice and rats and indicate the dependence of the pharmacological activity of the BDNF mimetic on animal age.

Resveratrol: A Multifaceted Guardian against Anxiety and Stress Disorders-An Overview of Experimental Evidence.

The medicinal properties of resveratrol have garnered increasing attention from researchers. Extensive data have been accumulated on its use in treating cardiovascular diseases, immune system disorders, cancer, neurological diseases, and behavioral disorders. The protective mechanisms of resveratrol, particularly in anxiety-related stress disorders, have been well documented. However, less attention has been given to the side effects of resveratrol. This review explores not only the mechanisms underlying the anxiolytic effects of resveratrol but also the mechanisms that may lead to increased anxiety following resveratrol treatment. Understanding these mechanisms is crucial for enhancing the efficacy of resveratrol in managing anxiety disorders associated with stress and PTSD.

The modulatory effects of tyrosol and nano-tyrosol on anxiety-like behavior and emotional memory in streptozotocin-induced diabetic rats.

The effects of tyrosol and nano-tyrosol on the modulation of anxiety-like behavior and memory processes were evaluated in streptozotocin-induced diabetic rats. Male diabetic rats were orally treated with 1 ml of saline, nano-niosome, tyrosol, and nano-tyrosol (20 mg/dl) for 30 days. Anxiety-like behavior and memory process were evaluated by an elevated plus-maze (EPM) test-retest paradigm. The results showed that a single intraperitoneal (i.p.) administration of streptozotocin (50 mg/kg) raised blood glucose. While daily intragastric administration of tyrosol and nano-tyrosol reduced blood glucose. Induction of type II diabetes produced a distorted cellular arrangement whereas treatment with tyrosol and nano-tyrosol showed a typical cellular arrangement in the liver. Furthermore, induction of type II diabetes decreased %OAT (%open-arm time) but daily intragastric application of tyrosol (20 mg/dl) and nano-tyrosol (20 mg/dl) enhanced %OAT and %OAE (%open-arm entry) in the EPM when compared to the saline groups, showing anxiogenic- and anxiolytic-like effects, respectively. Also, induction of type II diabetes increased %OAT while daily intragastric administration of tyrosol (20 mg/dl) and nano-tyrosol (20 mg/dl) decreased %OAT and %OAE in the EPM in comparison to the saline groups, displaying impairment and improvement of emotional memory, respectively. Interestingly, nano-tyrosol exhibited the highest significant effect rather than tyrosol. Upon these results, we proposed the beneficial effects of tyrosol and nano-tyrosol on the modulation of anxiety-like behavior and memory processes in streptozotocin-induced diabetic rats.

Repositioning pinacidil and its anticonvulsant and anxiolytic properties in murine models.

Epilepsy, frequently comorbid with anxiety, is a prevalent neurological disorder. Available drugs often have side effects that hinder adherence, creating a need for new treatments. Potassium channel activators have emerged as promising candidates for treating both epilepsy and anxiety. This study aimed to evaluate the potential anticonvulsant and anxiolytic effects of pinacidil, an ATP-sensitive potassium channel activator used as antihypertensive, in rats. Our results indicate that pinacidil at 10 mg/kg (i.p.) fully protected animals from seizures induced by pentylenetetrazol (PTZ) and provided 85.7%, 100% and 100% protection against pilocarpine-induced seizures at 2.5, 5 and 10 mg/kg (i.p.), respectively. Although the 2.5 and 5 mg/kg (i.p) doses did not significantly protect the animals from PTZ-induced seizures, they did significantly increase the latency to the first seizure. Pinacidil also demonstrated mild anxiolytic activity, particularly at 10 mg/kg (i.p), evidenced by increased time spent in the open or illuminated areas of the Elevated Plus Maze (EPM) and Light-Dark Box (LDB) and increased exploratory activity in the Open Filed, EPM and LDB. Pinacidil did not affect locomotor performance, supporting its genuine anticonvulsant effects. This study holds significant medical and pharmaceutical value by characterizing pinacidil's anticonvulsant and anxiolytic effects and highlighting its potential for therapeutic repositioning.

Neonatal limited bedding and nesting experience may lead to a sex-dependent increase in panic-like defensive behaviours in adult mice.

In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2-9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic-like escape behaviour was assessed during exposure to a high concentration of CO2 (20%) or in the beetle mania task (BMT), used to model respiratory and non-respiratory-related types of panic respectively. Neonatal exposure to LBN increased panic-like jumping during the CO2 challenge in male but not female mice. In an initial pharmacological validation of the BMT as a panic-inducing paradigm, undirected jumping and horizontal escape behaviours were reduced significantly by the panicolytic alprazolam (0.05 and 0.1mg.kg-1 i.p.) whilst tolerance to the close proximity of the aversive robo-beetle increased. The anxiolytic diazepam (1 mg.kg-1 i.p.) reduced only the number of horizontal escape attempts. In both sexes, previous experience of LBN significantly enhanced the number of horizontal escape episodes, indicating a pro-panic phenotype. Directed escape to access a safe ledge on the wall of the test arena, which was seen only in males, was also reduced significantly following LBN. These findings indicate that early life adversity produced by fragmented and unpredictable maternal care promotes a sex-specific increase in susceptibility to panic-like behaviour in adulthood. Whilst non-respiratory-related panic-like behaviour was enhanced in both sexes, females were resilient to respiratory-related challenges.

Anxiety disorders: Treatments, models, and circuitry mechanisms.

Anxiety disorders are one of the most prevalent mental health conditions worldwide, imposing a significant burden on individuals affected by them and society in general. Current research endeavors aim to enhance the effectiveness of existing anxiolytic drugs and reduce their side effects through optimization or the development of new treatments. Several anxiolytic novel drugs have been produced as a result of discovery-focused research. However, many drug candidates that show promise in preclinical rodent model studies fail to offer any substantive clinical benefits to patients. This review provides an overview of the diagnosis and classification of anxiety disorders together with a systematic review of anxiolytic drugs with a focus on their targets, therapeutic applications, and side effects. It also provides a concise overview of the constraints and disadvantages associated with frequently administered anxiolytic drugs. Additionally, the study comprehensively reviews animal models used in anxiety studies and their associated molecular mechanisms, while also summarizing the brain circuitry related to anxiety. In conclusion, this article provides a valuable foundation for future anxiolytic drug discovery efforts.

Comparative Study of the Anxiolytic Activity of Songorine in Elevated Plus Maze Test and by Recording Ultrasonic Vocalizations.

It was found that the diterpene alkaloid songorine administered per os to mice at a dose of 25 µg/kg provides a pronounced anxiolytic effect during elevated plus maze testing comparable to the effect of the benzodiazepine anxiolytic phenazepam. Recording of ultrasonic vocalizations of animals revealed an increase in the number of short high-frequency (50 kHz) signals under the action of songorine and the reference drug, which confirms their anti-anxiety properties.

Quality of life, pain and use of analgesic, anxiolytic and antidepressant medication, in people living in care homes.

BACKGROUND: People living in care homes often have problems with pain, anxiety and depression. Whether being on analgesia, anxiolytics or antidepressants has any bearing on pain severity and quality of life (QoL) in this population, requires further investigation. OBJECTIVES: (i) to examine the relationship between pain, anxiety and depression and medication use in care home residents and (ii) to compare those on medications to treat pain, anxiety and depression, and those who were not, and associations with pain severity and overall QoL. METHODS: This was a secondary analysis of a randomised controlled trial testing a falls prevention intervention in care homes. We recorded pain, anxiety and depression, QoL measurements and prescribed medication use. RESULTS: In 1589 participants, the mean age was 84.7 years (±9.3 SD), 32.2% were male and 67.3% had a diagnosis of dementia. 54.3% and 53.2% of participants had some level of pain and anxiety or depression respectively, regardless of prescribed medication use. There was a direct association between pain severity and being on any analgesia, opioid analgesia, and antidepressants, but no associations between pain severity and use of paracetamol and anxiolytics. QoL was best for residents with no pain and not on any analgesia, anxiolytics or antidepressants and worst for those with moderate-extreme pain and taking at least two of these classes of medications. CONCLUSION: Many care home residents live with pain, anxiety and depression. Addressing residents' pain may also increase their quality of life, but using medication alone to reach this goal may be inadequate.

Intranasal midazolam for procedural distress in children in the emergency department: a systematic review and meta-analysis.

OBJECTIVES: Intranasal (IN) midazolam is the most common anxiolytic for children in the emergency department (ED), but evidence of benefit is conflicting. We synthesized the evidence on IN midazolam for procedural distress in children undergoing ED painful procedures. METHODS: We included trials involving painful ED procedures in children 0-18 years involving IN midazolam. Primary outcome was procedural distress. We summarized results using Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," and "unfavorable" (p < 0.05), supporting IN midazolam or comparator, respectively, or "indeterminate" (unable to judge). Where possible, we pooled results using meta-analysis. Methodologic quality of evidence was evaluated using Cochrane Collaboration's risk of bias tool and GRADE system. RESULTS: We included 41 trials (n = 2973 participants). Thirty trials involved intravenous insertion. IN midazolam was superior to placebo (RR = 7.2; 95% CI: 3.43, 15.25; 3 trials; I2 = 0%). However, 56-90% of the IN midazolam group resisted the procedure. Focusing on the three trials that used validated measures, IN midazolam was "neutral" versus IN ketamine and either "neutral" or "unfavorable" versus IN dexmedetomidine. There was no difference in the proportion of children with a satisfactory distress score between IN midazolam and oral midazolam (RR = 1.1; 95% CI: 0.74, 1.73; 2 trials; I2 = 53%), IN ketamine (RR = 1.1; 95% CI: 0.91, 1.25; 6 trials; I2 = 0%), or IN dexmedetomidine (RR = 0.4; 95% CI: 0.17, 1.05; 3 trials; I2 = 84%). Ten trials involved laceration repair. IN midazolam was "favorable" versus placebo; however, both groups scored in the anxious range. There was no difference in distress between IN midazolam and oral midazolam (SMD = 0.01; 95% CI:-0.32, 0.34; 2 trials; I2 = 0%) (Fig. 3E) [64,65]. Using validated instruments, IN midazolam was "unfavorable" versus IN dexmedetomidine but "favorable" versus oral diazepam and placebo. CONCLUSIONS: There is limited methodologically rigorous evidence that IN midazolam is better than placebo for IV insertion and laceration repair. At the doses studied, preliminary evidence suggests that IN dexmedetomidine may be superior to IN midazolam for both IV insertion and laceration repair.

ABSTRAIT: OBJECTIFS: Le midazolam intranasal (IN) est l'anxiolytique le plus courant chez les enfants du service des urgences (DE), mais les preuves des avantages sont contradictoires. Nous avons synthétisé les preuves sur l'IN midazolam pour la détresse procédurale chez les enfants subissant des procédures douloureuses d'urgence. MéTHODES: Nous avons inclus des essais impliquant des procédures douloureuses d'urgence chez les enfants de 0 à 18 ans impliquant IN midazolam. Le résultat principal était la détresse procédurale. Nous avons résumé les résultats en utilisant la classification de Tricco et coll. de « neutre ¼ (p 0,05), « favorable ¼, « défavorable ¼ (p < 0,05), à l'appui du midazolam IN ou du comparateur, respectivement, ou « indéterminé ¼ (incapable de juger). Dans la mesure du possible, nous avons regroupé les résultats en utilisant la méta-analyse. La qualité méthodologique des preuves a été évaluée à l'aide de l'outil de risque de biais de Cochrane Collaboration et du système GRADE. RéSULTATS: Nous avons inclus 41 essais (n = 2973 participants). Trente essais portaient sur l'insertion intraveineuse. L'IN midazolam était supérieur au placebo (RR = 7,2; IC à 95 % : 3,43,15,25; 3 essais; I2 = 0 %). Cependant, 56 à 90 % du groupe IN midazolam a résisté à la procédure. En se concentrant sur les trois essais qui ont utilisé des mesures validées, IN midazolam était « neutre ¼ par rapport à IN kétamine et « neutre ¼ ou « défavorable ¼ par rapport à IN dexmedetomidine. Il n'y avait pas de différence dans la proportion d'enfants ayant un score de détresse satisfaisant entre IN midazolam et midazolam oral (RR = 1,1; IC à 95 % : 0,74,1,73; 2 essais; I2 = 53 %), IN kétamine (RR = 1,1; IC à 95 % : 0,91,1,25; 6 essais; I2 = 0 %) ou IN dexmedetomidine (RR = 0,4; IC à 95 % : 0,17,1,05; 3 essais; I2 = 84 %). Dix essais portaient sur la réparation de la lacération. L'IN midazolam était « favorable ¼ par rapport au placebo, mais les deux groupes ont obtenu des résultats dans la fourchette de l'anxiété. Il n'y avait pas de différence de détresse entre le midazolam IN et le midazolam oral (SMD = 0,01; IC à 95 %:-0,32,0,34; 2 essais; I2 = 0 %) (figure 3E)64,65. À l'aide d'instruments validés, l'IN midazolam était « défavorable ¼ par rapport à l'IN dexmedetomidine, mais « favorable ¼ par rapport au diazépam oral et au placebo. CONCLUSION: Il y a peu de preuves méthodologiques rigoureuses que l'IN midazolam est meilleur que le placebo pour l'insertion IV et la réparation de lacération. Aux doses étudiées, des preuves préliminaires suggèrent que l'IN dexmedetomidine peut être supérieure à l'IN midazolam pour l'insertion IV et la réparation de lacération.

[To study the effectiveness and impact on the quality of life of patients with subclinical and clinically pronounced anxiety disorder of a mobile application in combination with Adaptol therapy]. / Izuchenie effektivnosti i vliyaniya na kachestvo zhizni patsientov s subklinicheskim i klinicheski vyrazhennym trevozhnym rasstroistvom mobil'nogo prilozheniya v sochetanii s terapiei preparatom Adaptol.

OBJECTIVE: To study the effectiveness and the quality of life impact of the mobile application Zdorovye.ru in people with subclinical and clinical anxiety disorder (AD). MATERIAL AND METHODS: 200 patients with more than 7 points on the Hospital Anxiety and Depression Scale (HADS) were included. Participants were randomized into two groups: experimental one (EG, n=133) - to receive standard treatment with temgicoluril (Adaptol), 500 mg (Olainfarm JSC, Latvia) and the Zdorovye.ru application; control group (CG, n=52) - standard treatment with temgicoluril (Adaptol). RESULTS: There were a significant decrease in the HADS-A score, PSS-10 score and an increase in the visual analog scale EQ-5D score in both groups after 3 months of treatment (p<0.001). Clinical improvement was noticeable after 1.5 months in EG group: a decrease in HADS-A scores (p=0.001) and in tension and stress on PSS-10 subscales (p<0.001) were noted. This effect was not observed in the CG. After 3 months, all participants noted an improvement in quality of life (p<0.001), without a statistically significant difference between groups (p=0.233). The application left a positive impression on users and doctors - most respondents rated it as useful and clear. CONCLUSION: Taking temgicoluril (Adaptol) for 3 months led to symptoms decrease and the quality of life and well-being improvement in patients with AD. Using the mobile application Zdorovye.ru in conjunction with drug therapy made it possible to achieve a clinical effect earlier, in 1.5 months.

[Efficacy and safety of Aviandr in the treatment of anxiety in patients with adjustment disorders after COVID-19]. / Effektivnost' i bezopasnost' novogo preparata Aviandr v lechenii trevogi u patsientov s rasstroistvom adaptatsii posle perenesennoi ostroi koronovirusnoi infektsii.

OBJECTIVE: To investigate the efficacy and safety of Aviandr in the treatment of anxiety in patients with adjustment disorders after COVID-19. MATERIAL AND METHODS: A multicenter prospective open-label study included 109 patients of both sexes aged 18 to 65 years (70 women, 39 men, average age - 41.4±13.18 years) with a leading complaint of anxiety (Hamilton scale score, HAM-A ≥18 - ≤24), which arose after acute coronavirus infections. Clinical manifestations had to meet the diagnostic criteria F43.2 ICD-10. The drug Aviander was prescribed 20 mg 2 times a day for 4 weeks. At the end of taking the drug, patients were monitored for another 1 week (a delayed follow-up visit). Psychopathological, statistical and parametric research methods were used using standardized HAM-A, Montgomery-Asberg scales (MADRS), visual analog asthenia scale (VASH-A), Sheehan Disability Scale (SDS), digital character substitution test (DSST), general clinical impression scale (CGI). RESULTS: Data from 109\110 patients were analyzed to evaluate efficacy\safety. Aviandr was administered 20 mg 2 times daily for 4 weeks. Patients were followed for 1 week (delayed follow-up visit) at the end of treatment. Reducing the intensity of anxiety on the HAM-A scale was - 14.2±4.92 or 69.4±22.66% by the end of treatment. The response rate to therapy (responders are patients with a decrease in the total score on the HAM-A ≥50%) was 83.49%. Remission was achieved (sum of HAM-A scores ≤7) by the end of treatment 68.81% of patients, and 79.8% of patients at the follow-up visit. Significant changes were obtained on the MADRS, VAS-A, SDS and DSST scales. According CGI 45.9% of patients had «much improved¼ and 43.1% of patients had «very much improved¼ by the end of treatment; 58.7% of patients had «much improved¼ and of 33.9% patients had «very much improved¼ at the follow-up visit. 38 adverse events were reported in 27 (24.55%) patients during the study. A definite association with study drug was reported between 5 mild adverse events in 4 (3.64%) patients. No subjects withdrew from the study due to an adverse event. Positive dynamics (reduction of anxiety symptoms, decrease in asthenia) persisted after discontinuation of the study drug. No cases of withdrawal syndrome were observed. CONCLUSION: According to the results of the study, the anxiolytic, antidepressant, antiasthenic and pro-cognitive effects of Aviandr were observed. An increase in the social activity of patients was observed.

The effects of remimazolam in combination with estazolam on postoperative hemodynamics and pain intensity in patients undergoing laparoscopic gastrointestinal surgery.

OBJECTIVE: This study aimed to investigate the effects of combining remimazolam with estazolam on hemodynamics and pain levels after laparoscopic gastrointestinal surgery. METHODS: A total of 184 patients who underwent laparoscopic gastrointestinal surgery were enrolled in this double-blind randomized controlled trial. The patients were divided into four groups: Study Group 1(Remimazolam), Study Group 2(Estazolam), Study Group 3(Remimazolam + Estazolam), and Control Group. Anesthesia induction included intravenous injection of remimazolam and estazolam in the study groups, while the control group received normal saline. Hemodynamic parameters, stress responses, anxiety levels, and pain intensity were assessed at various time points. RESULTS: The results showed that the combination of remimazolam and estazolam significantly improved hemodynamic parameters compared to the control group. Study Group 3 exhibited the lowest anxiety levels and stress responses among all groups. Furthermore, Study Group 3 had the lowest pain intensity scores at different postoperative time points. CONCLUSION: The combination of remimazolam and estazolam effectively stabilized hemodynamics, reduced anxiety levels, and alleviated pain intensity after laparoscopic gastrointestinal surgery. These findings suggest that this combination therapy has the potential to improve surgical outcomes and patient comfort.

BEHAVIORAL AND NEUROCHEMICAL CHANGES DURING INTRANASAL ADMINISTRATION OF ALPHA-GLUTAMYL-TRYPTOPHAN AND CHELATE COMPLEX OF ZINC ARGINYL-GLYCINATE ON MONOAMINE SYSTEMS DYSFUNCTIONS KNOCK-OUT MODELS.

Monoamine neurotransmitter system dysfunctions lead to behavioral disorders, cognitive metabolic, and other pathological conditions. In this case, different amino acids are precursors of monoamines, while the parenteral path of monoamine administration has pharmacological restrictions. Therefore, intranasal administration one of the most promising methods of delivering an active substance is. The purpose of the work is to study the effect of intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide on behavioral and neurochemical changes in acute and chronic experiments. MATERIAL AND METHODS: The studies used outbred Wistar and DAT-KO rats, and inbred C57Bl6 and TAAR1-KO mice. Using intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide we tested methods for evaluating different behavioral indicators and the level of cerebral monoamines and their metabolites. RESULTS: An anxiolytic effect of zinc arginyl-glycinate and its combination with alpha-glutamyl-tryptophan was revealed. Both drugs have a physiological effect on the autonomic nervous system, but the determination of their operating mechanisms requires further research. CONCLUSION: Thus, these data indicate that intranasal delivery of the dipeptides is effective during acute and chronic intranasal administration in rodents, the latter showed a change in the anxiety indicator. Acute AG intranasal administration demonstrated signs of lower anxiety and depressive-like behavior in C57Bl6 mice. The acute intranasal administration of a chelate complex zinc arginyl-glycinate and combination with alpha-glutamyl-tryptophan in doses of 50-100 mg/kg of body weight may be used for pre-clinical studies as a new anxiolytic/antidepressant.

Anxiolytic treatment of a trapped rat reduces helping and anxiogenic treatment increases helping: Evidence for emotional contagion in altruism.

The present experiment used the trapped rat model to explore whether pharmacological manipulation of distress affects the likelihood of helping behavior. 120 Sprague-Dawley rats (30 male pairs and 30 female pairs) completed 12 consecutive, daily trials assessing helping behavior. During an individual trial, a trapped rat was placed in a restrainer in the center of an open field, while its cagemate could move around freely and possibly open the restrainer by lifting a door. Trapped rats received an intraperitoneal injection of either 1) physiological saline, 2) the anxiolytic midazolam (1.5 mg/kg), or 3) the anxiogenic yohimbine (2.5 mg/kg) 30 min prior to the start of each trial. Dependent variables measured were: 1) door opening latency (sec), 2) percentage of trials in which a door opening occurred, and 3) the number of free rats classified as "openers." Based on emotional contagion theory, we predicted that 1) free rats paired with midazolam-subjects would show attenuated helping behavior (e.g., higher door opening latency) compared to controls, and conversely 2) free rats paired with yohimbine-subjects would show enhanced helping behavior. First, a significant sex-difference was observed, in that more females were classified as openers than males. This supports previous evidence that females express higher altruistic motivation and experience stronger emotional contagion than males. Second, midazolam-treatment significantly attenuated helping behavior. From trials 4-12, free rats paired with midazolam-subjects expressed slower door opening latencies compared to controls. Third, yohimbine-treatment significantly increased helping behavior (e.g., reduced door opening latencies) - but only on trials 1-3; by trials 9-12, this pattern was reversed. These results are consistent with emotional contagion theory and indicate that intensity of distress directly modulates altruistic motivation through vicarious state-matching.