Structural Insights and Biological Activities of Furan-Based Drugs in the Treatment of Human Diseases.

Neurodegenerative diseases present significant public health challenges, driving the search for innovative therapeutic strategies. This review explores the neuroprotective potential of furan-containing compounds, which are derived from various natural and synthetic sources. These compounds are observed for their diverse pharmacological activities, including antioxidant and anti-inflammatory properties. By scavenging free radicals and mitigating oxidative stress, they address a key aspect of neurodegeneration. Additionally, furan derivatives modulate inflammatory pathways, potentially reducing neuroinflammation, a critical factor in the progression of these disorders. The review also highlights the impact of these compounds on neuronal survival and regeneration, suggesting their role in promoting neurogenesis and enhancing neuronal plasticity. Their interactions with neurotransmitter systems further support their neuroprotective effects, particularly in maintaining synaptic function and neurotransmission. The potential applications of furan-containing compounds are discussed concerning specific neurodegenerative diseases, such as Alzheimer's and Parkinson's. Insights from preclinical studies and in vitro experiments underscore their therapeutic promise across various experimental models. While still in the early stages of research, the evidence suggests that furan-containing compounds could be valuable in developing effective interventions for neurodegenerative diseases. This review emphasizes the need for further investigation into these compounds to realize their potential as neuroprotective agents fully.

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.

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.

Ameliorating effect of chotosan and its active component, Uncaria hook, on lipopolysaccharide-induced anxiety-like behavior in mice.

Introduction: In this study, we aimed to examine the effects of chotosan, a traditional Japanese botanical drug, and its active component, Uncaria hook, on anxiety-like behaviors induced by systemic inflammation in mice. Methods: To induce systemic inflammation, the mice were treated with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS treatment, the mice were administered chotosan or Uncaria hook orally each day for 14 days. Anxiety-like behavior of the mice was evaluated using the light-dark test 24 h after LPS treatment. Results: Repeated administration of chotosan prevented anxiety-like behavior in both normal and LPS-treated mice. Similarly, administration of Uncaria hook suppressed LPS-induced anxiety-like behavior in mice. Furthermore, treatment with tandospirone, a 5-HT1A receptor agonist, alleviated anxiety-like behavior in mice, whereas treatment with DOI, a 5-HT2A receptor agonist, enhanced anxiety-like behavior in mice. LPS treatment significantly increased serotonin (5-HT)2A receptor mRNA expression in the frontal cortex, whereas 5-HT1A receptor mRNA expression remained unchanged in the hippocampus. Notably, chotosan significantly suppressed the mRNA expression of 5-HT2A receptor. Discussion: These findings indicate that chotosan exerts anxiolytic-like effects in the context of inflammation-induced anxiety, potentially mediated by the inhibition of 5-HT2A receptor hyperfunction in LPS-treated mice. Consequently, we postulate that chotosan may be effective in managing inflammation-induced anxiety-like behaviors.

Interaction of age and sex as factors in understanding the anxiolytic effects of alcohol: Unasked questions limiting the understanding of a critical health issue.

Understanding the reasons why people consume alcohol is a critical health issue. Alcohol produces a variety of effects, including a reduction in stress or negative emotional states termed an anxiolytic effect. The anxiolytic effect of alcohol is an often-reported reason for why people begin consuming the drug. However, several factors concerning the stress-reducing effect of alcohol need to be investigated. For example, research has demonstrated that both age and sex are factors that impact alcohol's anxiolytic effect producing differential outcomes in aged female rats compared to aged male rats. In light of these findings, the current commentary highlights critical questions in need of research with the goal of better understanding how age and sex interact to influence the anxiolytic effect of alcohol. For example, the central nucleus of the amygdala has been identified as a critical brain region mediating the anxiolytic effect of drugs, but additional research is needed to understand how aging alters the neurological functioning of the central nucleus of the amygdala in both females and males. Furthermore, specific receptor isoforms, such as GABAA receptor α2, have been shown to be critical for anxiolysis and understanding how aging and sex alter receptor isoform expression by brain region is needed. Finally, age and sex interact to alter allopregnanolone levels in brain and differential neurosteroid levels may mediate alcohol's unique anxiolytic effect in aged female rats compared to aged male rats. Given the increasing age of the population in most countries and the increasing alcohol consumption levels in females compared to males, investigating the interaction of sex and age on alcohol's anxiolytic effect has great promise to discover critical answers to what are currently unasked questions.

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.

The anxiolytic-like effect of the alkaloid fraction of the psychedelic plant Mimosa tenuiflora (Willd.) Poir.

The present work investigated the anxiolytic effect of the alkaloid fraction (AF II) from the root bark of Mimosa tenuiflora. Female Swiss mice of 6 weeks old were used in this study. The animals were divided into three groups: 0.9% NaCl (vehicle group, s.c.), AF II (6 mg/kg, s.c.), and diazepam - DZP (5 mg/kg, s.c.). The light/dark box and elevated plus maze tests evaluated the animal anxiety. DMT was identified by the HPLC method. AF II showed significant anxiolytic effects in the two behavioural tests used.

Crotalaria quinquefolia L. Revealed as a Potential Source of Neuropharmacophore in Both Experimental and Computational Studies.

Herbal remedies have shown great promise for improving human health. The plant Crotalaria quinquefolia is used in folk medicine to cure different diseases, including scabies, fever, discomfort, and lung infections. The present research was designed to explore bioactive compounds and evaluate the neuropharmacological effects of C. quinquefolia through in vivo and in silico approaches. Different secondary metabolites as well as the antioxidant activity were measured. Furthermore, chemical compounds were identified by HPLC and GCMS analysis. The neuropharmacological activity was examined by hole cross, hole board, open field, Y-maze, elevated plus maze, and thiopental sodium induced sleeping time tests in mice at doses of 100 mg/kg and 200 mg/kg body weight. Besides, an in-silico study was performed on proteins related to Alzheimer disease. The extract showed a significant content of secondary metabolites and antioxidant potential. The in-silico analysis showed that myricetin, quercetin, rutin, and kaempferol have good binding affinity with studied proteins, and QSAR studies revealed potential benefits for treating dementia, age-related macular degeneration, and more. The findings of the present neurological activity collectively imply that the extract has strong CNS depressant and anxiolytic activity. Therefore, C. quinquefolia can be a potential source of secondary metabolites to treat Alzheimer disease.

Identification of different extracts and phytoconstituents of Callistemon viminalis Cheel for their anti-anxiety effects based on pharmacognostic, toxicological, and pharmacological strategies.

Background: Psychiatric disorders like depression and anxiety are global challenges, exacerbated by the limitations of synthetic medications, including addiction and toxic side effects. Methods: This study meticulously investigated the pharmacognostic, phytochemical, toxicological, and pharmacological properties of Callistemon viminalis Cheel. Toxicological assessments, including hemocompatibility assays, LD50 studies, FOB analysis, biochemical parameters, and structural integrity of vital organs, were conducted on aqueous, methanolic, chloroform, and petroleum ether extracts of leaves and stems. Phytochemical profiling via qualitative tests and GC-MS screened extracts for molecular docking against key receptors. Categorically screened extracts were evaluated for therapeutic potential against LPS-induced anxiety in mice. Results: Toxicological evaluations on experimental animals demonstrated the safety of various extracts, evidenced by no in vitro and in vivo toxicity. GC-MS identified numerous phytochemicals that passed "Lipinski's Rule of Five." These compounds were screened for molecular docking, revealing significant binding affinities with CB1, SERT, α2A-AR, and GABAß2 receptors, suggesting potential therapeutic effects against anxiety. The phytoconstituents with the highest docking scores, particularly in aqueous and methanolic extracts, were further validated for their therapeutic efficacy. Preliminary analysis based on the EPM test and serum cortisol levels confirmed these extracts' superior therapeutic effectiveness. Conclusion: In conclusion, aqueous and methanolic extracts of Callistemon viminalis Cheel's leaf and stem showed promising potential as therapeutic interventions for anxiety disorders.

ANXIOLYTICS: Origins, drug discovery, and mechanisms.

Anxiety is a part of the human condition and has been managed by psychoactive substances for centuries. The current medical need and societal demand for anxiolytic medicines has not abated. The present overview provides a brief historical introduction to the discovery of modern age anxiolytics that include the benzodiazepines together with a discussion of the continuing medical need for new antianxiety medications. The paper also discusses the use and impact of behavioral pharmacology in the preclinical development of anxiolytics. The review then highlights the diversity of mechanisms for creating a new generation of anxiolytics through mechanisms beyond the potentiation of GABAA receptors and the blockade of monoamine uptake. A discussion then follows on the behavioral specificity of action of anxiolytics that includes the concept of creating an anxioselective drug, one that targets anxiety without producing untoward effects that include sedation and dependence. The use of anxiolytics in the treatment of other conditions such as substance use disorder is also briefly reviewed. Finally, a brief summary of the current status of anxiolytic drug development is provided. The review concludes with the idea that despite a host of anxiolytic drugs, the lack of efficacy in some patients and the side-effects and safety issues associated with some of these medications demands alternative medicines. Current preclinical and clinical research is ongoing with the goal of identifying such compounds.

Research Letter: Dispensing of psychotropic medications in Australia between 2013 and 2022.

OBJECTIVE: The objective of this study was to determine the proportion of Australians dispensed psychotropic medications between 2013 and 2022 according to their age. METHODS: Services Australia provided a de-identified 10% random Pharmaceutical Benefits Scheme sample that allowed us to determine, for each year, the proportion of Australians dispensed at least one script for antipsychotics, antidepressants, anxiolytics, or hypnotics. The classification of medications followed Anatomical Therapeutic Chemical coding. Participants were stratified into 10-year age groups from 0-9 to ⩾90 years, and sex was coded as male/female. We retrieved population numbers from the Australian Bureau of Statistics. RESULTS: The number of records per year ranged from 1,540,520 to 1,746,402, and 54.10% were for females. A greater proportion of older adults, particularly those aged ⩾70 years, were dispensed antipsychotics, antidepressants, anxiolytics and hypnotics than any other age group. The proportion of people who dispensed antipsychotics, anxiolytics and hypnotics declined between 2013 and 2022 but increased for antidepressants, most markedly for adolescents and young adults. Females were more frequently dispensed antidepressants, anxiolytics and hypnotics than males, but males were more frequently dispensed antipsychotics than females, albeit not in later life. CONCLUSION: Older age groups and females are the most frequent recipients of psychotropic medications dispensed in Australia.

Auricular point acupressure for managing postoperative pain and reducing anxiety in patients with perianal abscesses.

OBJECTIVE: The objective of this study is to assess the efficacy of auricular point acupressure in relieving postoperative pain and reducing anxiety among patients with perianal abscesses. METHODS: We included 61 patients with perianal abscesses who were admitted to the Nantong First People's Hospital between July 2019 and June 2020 and were scheduled to undergo one-stage radical surgery. We divided them into the treatment group (n = 31), where patients were administered preoperative auricular acupressure targeting the bilateral Shenmen, subcortical, and other points. They were instructed to apply pressure five to six times per day, each time for about 3-5 min. Patients in the control group (n = 30) received routine preoperative preparation. The treatment duration for both groups was one week. We compared the two groups using the pain visual analog scale (VAS) scores, the use of additional postoperative analgesics, and scores on the Hamilton anxiety and depression scales pre- and post-surgery at 6 h, 24 h, 48 h, 72 h, and 1 week after surgery, as well as at the time of the first bowel movement. RESULTS: Patients in the treatment group reported lower VAS scores than those of the control group at 48 h, 72 h, 1 week, and at the first defecation post-surgery, and the differences were statistically significant (all P < 0.05). Additional postoperative analgesics were used in seven patients in the treatment group (22.58 %) and in 10 patients in the control group (33.33 %). The difference between the two groups was not statistically significant (χ2 = 0.88, P = 0.35). Postoperative scores for the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D) in the treatment group were significantly lower than those in the control group (P < 0.05). CONCLUSION: The results of this study demonstrated that auricular point acupressure was effective in alleviating postoperative pain in patients with perianal abscesses and simultaneously reduced their postoperative psychological stress reactions. This dual effect provided both pain relief and a reduction of anxiety with fewer adverse reactions, making it a safe and effective treatment option.

Melanin-concentrating hormone receptor: A therapeutic target for novel anxiolytics.

Anxiety disorders are chronic, disabling psychiatric disorders, and there is a growing medical need for the development of novel pharmacotherapeutic agents showing improved efficacy and an improved side effect profile as compared with the currently prescribed anxiolytic drugs. In the course of the search for next-generation anxiolytics, neuropeptide receptors have garnered interest as potential therapeutic targets, underscored by pivotal roles in modulating stress responses and findings from animal studies using pharmacological tools. Among these neuropeptide receptors, the type 1 receptor for melanin-concentrating hormone (MCH1), which has been demonstrated to be involved in an array of physiological processes, including the regulation of stress responses and affective states, has gained attraction as a therapeutic target for drugs used in the treatment of psychiatric disorders, including anxiety disorders. To date, a plethora of MCH1 antagonists have been synthesized, and studies using MCH1 antagonists and genetically manipulated mice lacking MCH1 have revealed that the blockade of MCH1 produces anxiolytic-like effects across diverse rodent paradigms. In addition, MCH1 antagonists have been demonstrated to show a rapid onset of antidepressant-like effects; therefore, they may be effective for conditions commonly encountered in patients with anxiety disorders, which is an advantage for anxiolytic drugs. Notably, MCH1 antagonists have not manifested the undesirable side effects observed with the currently prescribed anxiolytics. All these preclinical findings testify to the potential of MCH1 antagonists as novel anxiolytics. Although there are still issues that need to be resolved prior to the initiation of clinical trials, such as elucidating the precise neuronal mechanisms underlying their anxiolytic effects and exploring pertinent biomarkers that can be used in clinical trials, MCH1 blockade appears to be an attractive way to tackle anxiety disorders.

An investigation on the role of oxytocin in chronic neuropathic pain in a Wistar rat model.

Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect with ineffective preventative and curative treatment. Currently, only Duloxetine has been recommended as effective treatment for CIPN, which has shown individual-dependent, short-term analgesic effects, with limiting adverse effects and poor bioavailability. The neuropeptide, oxytocin, may offer significant analgesic and anxiolytic potential, as it exerts central and peripheral attenuating effects on nociception. However, it is unknown whether the intervention administered in a model of CIPN is an effective therapeutic alternative or adjuvant. Materials and Methods The intervention was divided into two phases. Phase 1 aimed to induce CIPN in adult Wistar rats using the chemotherapeutic agent Paclitaxel. Mechanical (electronic von Frey filament) and thermal (acetone evaporation test and Hargreaves test) hypersensitivity testing were used to evaluate changes due to the neuropathic induction. Phase 2 consisted of a 14-day intervention period with saline (o.g.), duloextine (o.g.), or oxytocin (i.n.) administered as treatment. Following the intervention, anxiety-like behaviour was assessed using the elevated plus maze (EPM) and light-dark box protocols. Analysis of peripheral plasma corticosterone, peripheral plasma oxytocin, and hypothalamic oxytocin concentrations were assessed using ELISA assays. Results The findings showed that we were able to successfully establish a model of chemotherapy-induced peripheral neuropathy during Phase 1, determined by the increase in mechanical and thermal nociceptive responses following Paclitaxel administration. Furthermore, the animals treated with oxytocin displayed a significant improvement in mechanical sensitivity over the intervention phase, indicative of an improvement in nociceptive sensitivity in the presence of neuropathic pain. Animals that received Paclitaxel and treated with oxytocin also displayed significantly greater explorative behaviour during the EPM, indicative of a reduced presence of anxiety-like behaviour. Conclusion Our results support the hypothesis that intranasally administered oxytocin may augment the analgesic and anxiolytic effects of duloxetine in a chemotherapy induced peripheral neuropathy model in a Wistar rat. Future studies should consider administering the treatments in combination to observe the potential synergistic effects.

Site specific binding pattern of benzodiazepines with GABAA receptor and related impact on their activities in the human body: An in silico method based study.

Despite of being the drugs of the same therapeutic class (Benzodiazepines), each of them shows different actions prominently. It is commonly seen that Bromazepam, Clonazepam, and, Alprazolam are prescribed for the treatment of anxiety disorders, panic disorders, and phobias. On the other hand, Midazolam, Temazepam, Flurazepam, and Nitrazepam are indicated for the treatment of insomnia and Lorazepam is considered as a drug having anticonvulsant effects. As the mechanism of action is the same, there should be some differences in the binding patterns with the proteins that create differences in their impacts on the body. A deep screening of the binding patterns of the available Benzodiazepines in the market to the GABAA receptor will be beneficial to find out the responsible amino acids for being accountable for showing any specific action. This reveal will help design new molecules with the highest beneficial effect and lowest toxicity in the body. The in silico method provides the initial level of understanding regarding the binding patterns, performing in vitro and in vivo experiments will be more specific to claim the benefits of newly designed drugs.

Exercise and Anxiety.

Anxiety disorders are among the most commonly diagnosed mental health disorders in the United States - affecting over 40 million adults per year. Although anxiety disorders are commonly treated via psychotherapy and/or pharmacotherapy, there is also accumulating evidence to suggest that physical activity and exercise may play an important role in prevention and treatment. This chapter provides an extensive overview of literature examining the effects of physical activity, acute bouts of exercise, and chronic exercise training on several anxiety outcomes, primarily in adults. The collective evidence to date suggests that: (1) an acute bout of aerobic or resistance exercise generally results in reductions in state anxiety among adults with and without clinical anxiety disorders, (2) greater levels of physical activity are associated with fewer anxiety symptoms and a reduced likelihood of developing an anxiety disorder, (3) exercise training (aerobic and resistance) appears to reduce general anxiety symptoms in adults without a clinical anxiety disorder and adults with a chronic illness (e.g., cardiovascular disease) and may reduce disorder-specific symptoms of anxiety in adults with a clinical anxiety disorder. Although the collective body of evidence is promising, there is a need for additional well-designed and adequately powered randomized controlled trials, especially among adults with clinical anxiety disorders.

Putative Pharmacological Depression and Anxiety-Related Targets of Calcitriol Explored by Network Pharmacology and Molecular Docking.

Depression and anxiety disorders, prevalent neuropsychiatric conditions that frequently coexist, limit psychosocial functioning and, consequently, the individual's quality of life. Since the pharmacological treatment of these disorders has several limitations, the search for effective and secure antidepressant and anxiolytic compounds is welcome. Vitamin D has been shown to exhibit neuroprotective, antidepressant, and anxiolytic properties. Therefore, this study aimed to explore new molecular targets of calcitriol, the active form of vitamin D, through integrated bioinformatic analysis. Calcitriol targets were predicted in SwissTargetPrediction server (2019 version). The disease targets were collected by the GeneCards database searching the keywords "depression" and "anxiety". Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the intersections of targets. Network analyses were carried out using GeneMania server (2023 version) and Cytoscape (V. 3.9.1.) software. Molecular docking predicted the main targets of the network and Ligplot predicted the main intermolecular interactions. Our study showed that calcitriol may interact with multiple targets. The main targets found are the vitamin D receptor (VDR), histamine H3 receptor (H3R), endocannabinoid receptors 1 and 2 (CB1 and CB2), nuclear receptor NR1H3, patched-1 (PTCH1) protein, opioid receptor NOP, and phosphodiesterase enzymes PDE3A and PDE5A. Considering the role of these targets in the pathophysiology of depression and anxiety, our findings suggest novel putative mechanisms of action of vitamin D as well as new promising molecular targets whose role in these disorders deserves further investigation.

Ligands of the trace amine-associated receptors (TAARs): A new class of anxiolytics.

Most cases of anxiety are currently treated with either benzodiazepines or serotonin reuptake inhibitors. These drugs carry with them risks for a multitude of side effects, and patient compliance suffers for this reason. There is thus a need for novel anxiolytics, and among the most compelling prospects in this vein is the study of the TAARs. The anxiolytic potential of ulotaront, a full agonist at the human TAAR1, is currently being investigated in patients with generalized anxiety disorder. Irrespective of whether this compound succeeds in clinical trials, a growing body of preclinical literature underscores the relevance of modulating the TAARs in anxiety. Multiple behavioral paradigms show anxiolytic-like effects in rodents, possibly due to increased neurogenesis and plasticity, in addition to a panoply of interactions between the TAARs and other systems. Crucially, multiple lines of evidence suggest that the TAARs, particularly TAAR1, TAAR2, and TAAR5, are expressed in the extended amygdala and hippocampus. These regions are central in the actuation of anxiety, and are particularly susceptible to neurogenic and neuroplastic effects which the TAARs are now known to regulate. The TAARs also regulate the dopamine and serotonin systems, both of which are implicated in anxiety. Ligands of the TAARs may thus constitute a new class of anxiolytics.

The anxiolytic effects of cannabinoids: A comprehensive review.

Cannabinoids, notably cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), have emerged as promising candidates for anxiety disorder treatment, supported by both preclinical and clinical evidence. CBD exhibits notable anxiolytic effects with a favourable safety profile, though concerns regarding mild side effects and drug interactions remain. Conversely, THC, the primary psychoactive compound, presents a range of side effects, underscoring the importance of careful dosage management and individualized treatment strategies. So far there are no FDA approved cannabinoid medications for anxiety. The review highlights challenges in cannabinoid research, including dosage variability, variable preclinical data, and limited long-term data. Despite these limitations, cannabinoids represent a promising avenue for anxiety management, with the potential for further optimization in formulation, dosing protocols, and consideration of interactions with conventional therapies. Addressing these challenges could pave the way for novel and personalized approaches to treating anxiety disorders using cannabinoid-based therapies.

The Study of TRPV1 Channels of the Central Nervous System and Their Effect on Anxiety in ICR Mice.

The TRPV1 channel is actively involved in various neuronal processes and is found in various structures of the nervous system, including peripheral and central neurons, sensory ganglia, spinal cord, and various parts of the brain. Due to its ability to respond to various stimuli, TRPV1 can have a significant impact on the body's responses to stress. Studies indicate the involvement of TRPV1 in the regulation of anxiety behavior. Suppression of TRPV1 activity leads to a decrease in the level of anxiety in animals, which indicates the importance of this channel in psychoemotional regulation. A promising compound for inhibiting this channel is the APHC3 peptide, which is a selective receptor antagonist. The results obtained this study show that this peptide has a pronounced anxiolytic effect, reducing the level of anxiety in the studied animals.