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Polyelectrolyte multilayer (PEM) was developed through layer-by-layer (LbL) adsorption on sodium alginate on negatively charged lipid polymer hybrid nanoparticles (LPHNPs) for the delivery of Buspirone hydrochloride (BUH). The resultant BUH-LPHNPs (F2) showed a mean particle size of 166 ± 4.2 nm and zeta potential of −30.5 ± 1.52 mV. The BUH-LPHNPs were found to be stable and demonstrated controlled drug release kinetics. Further, the pharmacokinetic studies revealed a 3.29-fold rise in the oral bioavailability of formulation (F2) than BUH (pure). Thus, PEM fabricated through LbL technology could be explored for overcoming the bioavailability issue and targeted delivery for potential drug candidates. [ABSTRACT FROM AUTHOR]

Abstract In recent years, buspirone has been co-administered with sertraline to resolve sexual disorders caused by sertraline. Therefore, the present study was conducted to investigate the interaction effect of two antidepressants and anxiolytic drugs, sertraline and buspirone, on human serum albumin (HSA) using spectroscopic and molecular docking techniques. Fluorescence emission spectroscopy and molecular docking were used to calculate the binding affinity and determine the best binding sites for these two drugs. Additionally, UV-visible and circular dichroism spectroscopy were performed to investigate the effect of these drugs on the conformational changes of HSA. The results showed that both drugs have a strong ability to quench the fluorescence of HSA through a static mechanism, and cause structural changes in HSA. It was also found that binding of sertraline and buspirone to HSA is spontaneous (ΔG°

Functional dizziness (FD) is the most common form of chronic dizziness, accounting for up to 20% of all cases of chronic dizziness and is diagnosed in 40% of patients referred to specialized clinics. This article discusses the pathogenesis, clinical manifestations and diagnostic features of FD. An overview of standard and new methods of drug therapy and methods of vestibular rehabilitation for patients with FD is provided. Experts conclude that FD, currently defined as persistent postural perceptual dizziness (PPPD), is the most common cause of chronic non-rotational dizziness. PPPD is thought to be multifactorial; central and peripheral vestibular disorders, anxiety disorders and traumatic brain injury are noted as possible precipitating causes. The diagnosis of PPPD is based on the presence of a feeling of unsteadiness or non-rotational dizziness occurring more than half of the days over a period of three months or longer, when other possible causes of dizziness have been ruled out. When managing a patient with PPPD, it is necessary to inform the patient about the nature of the disease, provide a patient with an education program and apply psychotherapy and vestibular rehabilitation methods. The use of buspirone prolonged-release tablets (Vespirate®) and vestibular rehabilitation in clinical practice is discussed.

Purpose: Buspirone, an anxiolytic with minimal risk of dependence or respiratory depression, lacks extensive published data on its transfer into human milk during lactation. The objective of this study was to 1) quantify the transfer of buspirone and its active metabolite 1-pyrimidinylpiperazine (1-PP) into human milk, allowing for an estimation of maternal drug exposure to the breastfed infant, and 2) report observations of the infants exposed to buspirone via breastmilk. Methods: Milk samples and health histories were collected from nine lactating mothers who donated milk samples to the InfantRisk Human Milk Biorepository while taking buspirone. The drug concentration–time profile of buspirone and 1-PP was determined using liquid chromatography–mass spectrometry. Results: Buspirone was below the detection level of 1.5 ng/mL in all milk samples with dosages ranging from 7.5 to 30 mg twice daily. However, low levels of active metabolite 1-PP were observed at 7.5 mg twice daily up to 30 mg twice daily. The relative infant dose (RID) calculated ranged from 0.21 to 2.17%, which is below the standard 10% threshold for infant safety. There were no reports of adverse effects in the exposed infants. Conclusion: The levels of buspirone observed in all participants' milk samples were exceedingly low. The subsequently low relative infant dose (RID) in the range of 0.21% to 2.17% is below the 10% threshold for infant safety, suggesting that the transfer of maternal buspirone and its active metabolite (1-PP) into human milk is clinically insignificant and poses minimal risk to a breastfed infant. [ABSTRACT FROM AUTHOR]

Background: Anxiety is one of the common mental disorders. Non-fatal health loss is one of the consequences of anxiety disorders. Oxidative stress may also play a role in anxiety disorders. As an antioxidant, Vitamin C can create stable ascorbate free radicals and lower reactive oxygen species. In addition, Vitamin C can prevent damage caused by free radicals. Oxidative stress can also lead to depression, schizophrenia, and bipolar disorder. Aim and Objectives: The aim and objectives of the study are to compare the antianxiety effects of Vitamin C, buspirone, and diazepam in albino rats using elevated plus maze and hole board apparatus. Materials and Methods: 36 albino rats of either sex were divided into 6 groups of 6 rats each and drugs were administered orally. Group 1 received distilled water 10 ml/kg, Group 2 received Vitamin C 200 mg/kg, Group 3 received buspirone 10 mg/kg, Group 4 received diazepam 1 mg/kg, Group 5 received buspirone 10 mg/kg + Vitamin C 200 mg/kg, and Group 6 received diazepam 1 mg/kg + Vitamin C 200 mg/kg. Antianxiety effects of these drugs were tested after 14 days of drug administration using hole board apparatus and elevated plus maze. The methods used for statistical analysis were mean, standard deviation, confidence interval, median, interquartile range (IQR), frequency and percentage, ANOVA, Kruskal-Wallis test, and Fisher's exact test. Results: On average time spent in open arms by Group 5 was 98.00 sec (IQR: 19.75-138.00) which was higher than other groups, but it was not statistically significant (P = 0.845). The time spent in closed arms in seconds by Group 4 was 245 ± 28.863, which was higher than other groups, but it was not statistically significant (P = 0. 805). On average head dip by Group 5 was 9.83 ± 4.708, which was higher than other groups, but it was not statistically significant (P = 0.141). Conclusion: Group 5 rats that received buspirone and Vitamin C, followed by Group 6 rats that received diazepam and Vitamin C had spent more time and had more entries into the open arms. Furthermore, Groups 5 and 6 animals had a greater number of head dips in the hole board apparatus compared to the behavior of all animals in other groups. Buspirone and diazepam are known anxiolytics. When these drugs were given in combination with Vitamin C, the antianxiety behaviors in rats were more compared to the drugs given alone in the present study but it was not statistically significant. [ABSTRACT FROM AUTHOR]

The heterogeneity of etiology may serve as a crucial factor in the challenges of treatment, including the low response rate and the delay in establishing therapeutic effect. In the present study, we examined whether social experience since early life is one of the etiologies, with the involvement of the 5-HT1A receptors, and explored the potentially therapeutic action of the subchronic administration of buspirone, a partial 5-HT1A agonist. Rats were isolation reared (IR) since their weaning, and the depressive profile indexed by the forced-swim test (FST) was examined in adulthood. Nonspecific locomotor activity was used for the IR validation. Buspirone administration (1 mg/kg/day) was introduced for 14 days (week 9–11). The immobility score of the FST was examined before and after the buspirone administration. Tissue levels of serotonin (5-HT) and its metabolite 5-HIAA were measured in the hippocampus, the amygdala, and the prefrontal cortex. Efflux levels of 5-HT, dopamine (DA), and norepinephrine (NE) were detected in the hippocampus by brain dialysis. Finally, the full 5-HT1A agonist 8-OH-DPAT (0.5 mg/kg) was acutely administered in both behavioral testing and the dialysis experiment. Our results showed (i) increased immobility time in the FST for the IR rats as compared to the social controls, which could not be reversed by the buspirone administration; (ii) IR-induced FST immobility in rats receiving buspirone was corrected by the 8-OH-DPAT; and (iii) IR-induced reduction in hippocampal 5-HT levels can be reversed by the buspirone administration. Our data indicated the 5-HT1A receptor-linked early life social experience as one of the mechanisms of later life depressive mood. [ABSTRACT FROM AUTHOR]

The current study evaluated the impact of buspirone supplementation on the growth, physiology, stress response, spawning, and immunity in female goldfish (Carassius auratus). For this purpose, buspirone was dissolved in absolute methanol and sprayed onto the feed to create four experimental groups: B0 (control), B25 (25 mg kg−1), B50 (50 mg kg−1), and B100 (100 mg kg−1). Fish were fed their respective diets for 56 days and subjected to stress using the air exposure method at the end of the experiment. Growth performance analysis revealed that fish in the B100 group exhibited significantly higher final weight, weight gain, specific growth rate, and average daily gain than the other groups (P

Buspirone is an anxiolytic agent. The most common side effect reported with the use of buspirone is dizziness. Movement disorders associated with buspirone were rarely described. A 20-year-old female was diagnosed with generalized anxiety disorder. She was started on buspirone, and the dose was progressively increased. Despite therapy, for 14 days, the patient did not report any improvement in symptoms, and the general practitioner increased the dosage to 10 mg three times a day. On day 28th of buspirone therapy, she reported progressive neck stiffness within one day of onset. On examination, right lateralization of the neck was seen. Laboratory tests, neuroimaging, and electroencephalogram were unremarkable. She was started on intravenous diphenhydramine. Within 2 hours, the symptoms improved. The subject retook the buspirone and developed the same symptoms. She was started on intravenous diphenhydramine, and symptomatic improvement was seen. Due to repeated instances of adverse drug events occurring, buspirone was discontinued. There are seven reports of dystonia secondary to buspirone in the literature. But, the present case of buspirone-induced dystonia is the first reported in a previously healthy patient. Clinicians should monitor motor symptoms when increased doses of buspirone are needed. In buspirone-induced dystonia, buspirone withdrawal and anticholinergic medications should be attempted.

Spatial learning, memory, and reactivity of the hypothalamic—pituitary—adrenocortical system (HPA axis) were studied in adult male rats, whose mothers during pregnancy were subjected to acute moderate normobaric hypoxia, or repeated injections of buspirone, an agonist of type 1A serotonergic receptors (5HT1A), or their combination. Prenatal treatment with buspirone in rats with prenatal hypoxia impaired learning ability during the first day of 5-day training. A decrease in the effectiveness of long-term memory in comparison with short-term memory was revealed in two groups of rats: prenatal treatment with buspirone in combination with hypoxia and injection of physiological saline without hypoxia. The effectiveness of long-term memory and the level of corticosterone in response to stress did not differ between the groups, which can indicate adaptation of the 5HT1A receptor and the HPA axis to the prenatal buspirone and normobaric hypoxia during ontogeny. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence suggests that co‐administration of the 5‐HT1A agonist buspirone and the 5‐HT1B/1D agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone. Objectives: Assess the therapeutic potential of a fixed‐dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa‐induced dyskinesia. Methods: Single‐center, randomized, placebo‐controlled, two‐way crossover study (NCT02439203) of a fixed‐dose buspirone/zolmitriptan regimen (10/1.25 mg three times a day) in 30 patients with PD experiencing at least moderately disabling peak‐effect dyskinesia. Results: Seven days of treatment with buspirone/zolmitriptan added to levodopa significantly reduced dyskinesia as assessed by Abnormal Involuntary Movement Scale scores versus placebo (mean treatment effect vs. placebo: −4.2 [−6.1, −2.3]) without significantly worsening Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON) scores (mean treatment effect vs. placebo: 0.6 [−0.1, 1.3]). No serious adverse events were reported. Conclusions: In this proof‐of‐concept study, addition of buspirone/zolmitriptan to the patients' PD medication regimen significantly reduced dyskinesia severity without worsening motor function. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

A proportion of farmed salmon in seawater show a behaviorally inhibited, growth stunted profile known as a depression-like state (DLS). These DLS fish are characterized by chronically elevated serotonergic signaling and blood plasma cortisol levels and the inability to react further to acute stress, which is suggestive of chronic stress. In this study, we characterize the neuroendocrine profile of growth stunted freshwater parr and confirm that they show a DLS-like neuroendocrine profile with a blunted cortisol response and no serotonergic increase in response to acute stress. Furthermore, we attempted to reverse this DLS-like profile through pharmacological manipulation of the serotonin (5-HT) system with buspirone, an anxiolytic medication that acts as a serotonin receptor agonist (i.e., decreases serotonergic signaling). We found that while buspirone decreases anxiolytic-type behavior in healthy fish, no quantifiable behavioral change was found in DLS-like fish. However, there was a physiological effect of diminished basal serotonergic signaling. This suggests that at the physiological level, buspirone appears to reverse the neuroendocrine DLS profile. With a deeper understanding of what causes DLS profiles and growth stunting in juvenile fish, steps can be taken in terms of husbandry to prevent repeated stressors and the formation of the DLS profile, potentially reducing losses in aquaculture due to chronic stress. [ABSTRACT FROM AUTHOR]

To screen modulators of biogenic amine (BA) neurotransmission for the ability to cause fentanyl to decrease isoflurane minimum alveolar concentration (MAC) in cats, and to test whether fentanyl plus a combination of modulators decreases isoflurane MAC more than fentanyl alone. Prospective, experimental study. A total of six adult male Domestic Short Hair cats. Each cat was anesthetized in three phases with a 1 week washout between studies. In phase 1, anesthesia was induced and maintained with isoflurane, and MAC was measured in duplicate using a tail clamp stimulus and standard bracketing technique. A 21 ng mL–1 fentanyl target-controlled infusion was then administered and MAC measured again. In phase 2, a single cat was administered a single BA modulator (buspirone, haloperidol, dexmedetomidine, pregabalin, ramelteon or trazodone) in a pilot drug screen, and isoflurane MAC was measured before and after fentanyl administration. In phase 3, isoflurane MAC was measured before and after fentanyl administration in cats co-administered trazodone and dexmedetomidine, the two BA modulator drugs associated with fentanyl MAC-sparing in the screen. Isoflurane MAC-sparing by fentanyl alone, trazodone–dexmedetomidine and trazodone–dexmedetomidine–fentanyl was evaluated using paired t tests with p < 0.05 denoting significant effects. The MAC of isoflurane was 1.87% ± 0.09 and was not significantly affected by fentanyl administration (p = 0.09). In the BA screen, cats administered trazodone or dexmedetomidine exhibited 26% and 22% fentanyl MAC-sparing, respectively. Trazodone–dexmedetomidine co-administration decreased isoflurane MAC to 1.50% ± 0.14 (p < 0.001), and the addition of fentanyl further decreased MAC to 0.95% ± 0.16 (p < 0.001). Fentanyl alone does not affect isoflurane MAC in cats, but co-administration of trazodone and dexmedetomidine causes fentanyl to significantly decrease isoflurane requirement. [ABSTRACT FROM AUTHOR]

Williams syndrome (WS) is a rare genetic disorder associated with a high prevalence of anxiety disorders. Evidence-based pharmacologic treatments for anxiety in WS are lacking. The purpose of this study is to provide naturalistic data on the use of buspirone for the treatment of anxiety in WS. Medical records of 24 individuals with Williams syndrome (ages 7–47 years) and anxiety who received treatment with buspirone were reviewed. Treatment response to buspirone was rated by assigning a retrospective Clinical Global Impression Improvement subscale (CGI-I) score. Twenty-three of 24 (96%) patients completed at least a 16-week treatment course with buspirone. Sixteen patients (67%; 95% CI 47%, 82%) were treatment responders (CGI-I ≤ 2). Only 1 (4%) patient discontinued buspirone due to a treatment-emergent side effect (nausea and vomiting). The most common side effect was nausea (13%). Twenty (84%) patients remained on buspirone at the time of their most recent follow-up visit. In this retrospective study, the majority of patients responded to a 16-week course of buspirone. Prospective studies are warranted to further assess the efficacy and tolerability of buspirone for anxiety in WS. [ABSTRACT FROM AUTHOR]

Chronic oxidative stress impairs the normal functioning of the retinal pigment epithelium (RPE), leading to atrophy of this cell layer in cases of advance age-related macular degeneration (AMD). The purpose of our study was to determine if buspirone, a partial serotonin 1A (5-HT1A) receptor agonist, protected against oxidative stress-induced changes in the RPE. We exposed differentiated human ARPE-19 cells to paraquat to induce oxidative damage in culture, and utilized a mouse model with sodium iodate (NaIO3)-induced oxidative injury to evaluate the effect of buspirone. To investigate buspirone's effect on protective gene expression, we performed RT–PCR. Cellular toxicities and junctional abnormalities due to paraquat induction in ARPE-19 cells and buspirone's impact were assessed via WST-1 assays and ZO-1 immunostaining. We used spectral-domain optical coherence tomography (SD-OCT) and ZO-1 immunostaining of RPE/choroid for structural analysis. WST-1 assays showed dose-dependent protection of viability in buspirone-treated ARPE-19 cells in culture and preservation of RPE junctional integrity under oxidative stress conditions. In the NaIO3 model, daily intraperitoneal injection (i.p.) of buspirone (30 mg/kg) for 12 days improved the survival of photoreceptors compared to those of vehicle-treated eyes. ZO-1-stained RPE flat-mounts revealed the structural preservation of RPE from oxidative damage in buspirone-treated mice, as well as in buspirone-induced Nqo1, Cat, Sqstm1, Gstm1, and Sod2 genes in the RPE/choroid compared to untreated eyes. Since oxidative stress is implicated in the pathogenesis AMD, repurposing buspirone, which is currently approved for the treatment of anxiety, might be useful in treating or preventing dry AMD. [ABSTRACT FROM AUTHOR]

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.

Buspirone, a 5-hydroxytryptamine 1A (5-HT1A) receptor agonist, has been investigated for its use in various diseases. However, knowledge about its side effects and potential cognitive benefits in different conditions is limited. Cognitive impairment is also a prevalent symptom in many diseases, yet effective treatments are still lacking. Therefore, to explore the potential side effects of buspirone and the possible cognitive benefits of buspirone, we conducted a comprehensive search of several databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. Our primary outcome measures included both side effects (adverse events) and cognitive benefits. For continuous variables, we utilized effect size with a 95% confidence interval (CI), whereas for dichotomous variables, we used odds ratios (OR) with a 95% CI. In total, 16 studies were included in this analysis, with 13 studies reporting on buspirone's side effects and 4 studies focusing on cognitive tasks. In terms of side effects, buspirone exhibited a higher rate of dizziness (OR = 4.66, 95% CI: 2.07–10.47), constipation (OR = 4.11, 95% CI: 1.34–12.55), and gastric distress (OR = 1.97, 95% CI: 1.03–3.78) than the placebo group. Regarding cognitive functions, buspirone showed significant benefits (g = 0.20, 95% CI: 0.06–0.34) while the placebo did not. Subgroup analysis indicated superior performance in visual learning and memory (g = 0.49, 95% CI: 0.21–0.78), logical reasoning (g = 0.42, 95% CI: 0.14–0.71), and attention (g = 0.37, 95% CI: 0.13–0.61) when compared to placebo. Our findings indicated that participants in the buspirone group experienced side effects of dizziness, constipation, and gastric distress in different diseases. Despite these adverse events, however, buspirone demonstrated significant cognitive benefits, particularly in the domains of visual learning and memory, logical reasoning, and attention.

Functional dizziness (FD) is one of the most common causes of chronic dizziness for which there is no effective drug therapy, highlighting the importance of searching for new treatment technologies.Objective: to evaluate the efficacy and safety of Vespireit® (INN buspirone) prolonged-release tablets 15 mg2 (JSC “Valenta Pharm”, Russia) compared with placebo in the treatment of patients with autonomic dysfunction syndrome accompanied by FD.Material and methods. The clinical trial (CT) included a total of 268 patients with autonomic dysfunction syndrome accompanied by FD and a DHI (The Dizziness Handicap Inventory) dizziness scale score of 36 to 52 inclusive, who were randomly divided into 2 groups and treated in a double-blind fashion. 135 patients (Group 1) received Vespireit® prolonged-release tablets 15 mg at a dose of 15 mg (1 tablet) once daily for 28 days. 133 patients (Group 2) received placebo at the same dosage regimen. Treatment was given against a background of vestibular gymnastic exercises. The primary outcome of the clinical trial was assessment of patient response rate (proportion of responders), i.e., a ≥50% reduction in total DHI for dizziness score at Visit 5 (day 28±1) compared with baseline (Visit 1, day 1). Secondary efficacy measures included assessment of: 1) treatment response rates (≥50% reduction in DHI total score compared to Visit 1) at Visits 2, 3, and 4; 2) DHI total score at Visits 2, 3, 4, and 5; 3) changes in DHI total score at Visits 2, 3, 4, and 5 compared to Visit 1; 4) proportion of patients with a 30% or greater reduction in DHI scale dizziness compared with baseline at Visit 2, 3, 4, and 5; 5) time elapsed until total DHI score decreased by ≥50% compared to baseline; 6) time elapsed until total DHI score decreased by ≥30% compared to baseline; 7) changes in Digital Rating Scale (DRS) score from Visit 1 to Visit 2, 3, 4, 5; 8) scores on the DRS at Visits 2, 3, 4, 5; 9) proportion of patients with different response to treatment on the Likert scale at Visits 2, 3, 4, and 5. Additional secondary criteria of efficacy were also assessed: total Hamilton Depression Rating Scale (HDRS) score at Visits 4 and 5; change in total Hamilton scale score at Visits 4 and 5 compared to Visit 1. The safety criterion assessed in the clinical trial was monitoring of adverse events (AEs), clinically significant deviations in vital signs, laboratory parameters, and ECG parameters.Results. The proportion of responders with a ≥50% reduction in DHI total score at Visit 5 (Day 28±1) compared to baseline (Visit 1, Day 1) was 68.7% (n=92) in Group 1, which was 52.9% more than in Group 2 – 15.8% (n=21) (p

Spinal cord stimulation enhanced restoration of motor function following spinal cord injury (SCI) in unblinded studies. To determine whether training combined with transcutaneous electrical spinal cord stimulation (tSCS), with or without systemic serotonergic treatment with buspirone (busp), could improve hand function in individuals with severe hand paralysis following SCI, we assessed ten subjects in a double-blind, sham-controlled, crossover study. All treatments-busp, tSCS, and the busp plus tSCS-reduced muscle tone and spasm frequency. Buspirone did not have any discernible impact on grip force or manual dexterity when administered alone or in combination with tSCS. In contrast, grip force, sinusoidal force generation and grip-release rate improved significantly after 6 weeks of tSCS in 5 out of 10 subjects who had residual grip force within the range of 0.1-1.5 N at the baseline evaluation. Improved hand function was sustained in subjects with residual grip force 2-5 months after the tSCS and buspirone treatment. We conclude that tSCS combined with training improves hand strength and manual dexterity in subjects with SCI who have residual grip strength greater than 0.1 N. Buspirone did not significantly improve the hand function nor add to the effect of stimulation.

The heterogeneity of etiology may serve as a crucial factor in the challenges of treatment, including the low response rate and the delay in establishing therapeutic effect. In the present study, we examined whether social experience since early life is one of the etiologies, with the involvement of the 5-HT1A receptors, and explored the potentially therapeutic action of the subchronic administration of buspirone, a partial 5-HT1A agonist. Rats were isolation reared (IR) since their weaning, and the depressive profile indexed by the forced-swim test (FST) was examined in adulthood. Nonspecific locomotor activity was used for the IR validation. Buspirone administration (1 mg/kg/day) was introduced for 14 days (week 9–11). The immobility score of the FST was examined before and after the buspirone administration. Tissue levels of serotonin (5-HT) and its metabolite 5-HIAA were measured in the hippocampus, the amygdala, and the prefrontal cortex. Efflux levels of 5-HT, dopamine (DA), and norepinephrine (NE) were detected in the hippocampus by brain dialysis. Finally, the full 5-HT1A agonist 8-OH-DPAT (0.5 mg/kg) was acutely administered in both behavioral testing and the dialysis experiment. Our results showed (i) increased immobility time in the FST for the IR rats as compared to the social controls, which could not be reversed by the buspirone administration; (ii) IR-induced FST immobility in rats receiving buspirone was corrected by the 8-OH-DPAT; and (iii) IR-induced reduction in hippocampal 5-HT levels can be reversed by the buspirone administration. Our data indicated the 5-HT1A receptor-linked early life social experience as one of the mechanisms of later life depressive mood.

Objective: to evaluate the pharmacokinetic parameters, safety and tolerability of Vespireit® (INN buspirone), prolonged-release tablets, 15 mg (JSC “Valenta Pharm”, Russia), which is being developed as a drug for the treatment of functional vertigo, in healthy volunteers with a single oral dose of 15 and 30 mg on an empty stomach or after meals and multiple doses in a daily dose of 15 mg.Material and methods. JSC “Valenta Pharm” conducted an open-label, three-stage, randomized, two-periods, cross-over comparative clinical trial of Vespireit®. At stages 1 and 2, healthy volunteers were screened and randomized into two equal groups (Group 1 and Group 2), as well as the distribution of participants in Group 3. Then, at stage 1, healthy volunteers (n=24) took Vespireit® once at a dose of 15 mg on an empty stomach or after meals, at stage 2, volunteers (n=24) took Vespireit® once at a dose of 30 mg on an empty stomach or after meals. Stage 3 was conducted in 18 volunteers as a non-randomized, non-comparative study with Vespireit® 15 mg on an empty stomach once daily for 5 days. During the study, blood samples were collected from each subject to determine the concentration of test compounds in blood plasma and subsequently calculate their pharmacokinetic parameters. Quantitative determination of buspirone and its two metabolites, 6-hydroxybuspirone (6OH-bus) and 1-(2-pyrimidinyl)-piperazine (1-PP), was performed by a validated high-performance liquid chromatography method with tandem mass spectrometric detection. During the study, tolerability and safety were also evaluated: adverse events, vital signs, laboratory parameters and electrocardiogram parameters were recorded.Results. When the study drug Vespireit®, prolonged-release tablets, was administered once at a dose of 15 mg to healthy volunteers after a meal, an increase in the relative bioavailability and relative degree of absorption of buspirone was observed compared with the fasting state, which was accompanied by a 1.5- and 2.5-fold increase in the AUC0–t and Cmax of buspirone, respectively. In addition, the Cmax of 6-OH-bus increased 1.4-fold and the Cmax of 1-PP increased 1.2-fold. Meal had no effect on the AUC0–t of 6-OH-bus and 1-PP. When the study drug was administered once at a dose of 30 mg after a meal, an increase in the relative bioavailability and relative degree of absorption of buspirone was observed compared with fasting, which was accompanied by an increase in the AUC0–t and Cmax by 1.5- and 2.1-fold, respectively. A 1.2-fold increase in the Cmax of 6-OH-bus was also observed. Food had no effect on the AUC0–t of 6-OH-bus and on the AUC0–t and Cmax of 1-PP. No accumulation of buspirone and its metabolites was observed with repeated dosing.Conclusion. In the study, the values of pharmacokinetic parameters of the new drug Vespireit® in the prolonged-release tablets dosage form were determined both with single administration on an empty stomach and after meals and with multiple administration. The differences and advantages over buspirone preparations in the form of immediate-release tablets are shown: higher relative bioavailability of buspirone with a reduction in interindividual differences in bioavailability and Cmax, more stable plasma concentration of buspirone with reduced peak values of the active substance and metabolite 1-PP, a 1.2-fold increase in AUC0–∞, a 2-fold increase in T1/2, and a 2-fold increase in the degree of retardation (MRT) for buspirone, a 1.4-fold increase in Cmax and MRT of 6-OH-bus, a decrease in AUC0–∞, AUC0–t, and T1/2 of metabolite 1-PP, and a decrease in the ratio of the concentration of 1-PP to the concentration of buspirone and to 6-OH-bus. A favorable safety profile of Vespireit® was demonstrated.

Rationale and objectives: Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear. Methods: Following a comprehensive search in Medline and Embase, we included 68 research articles that reported on 103 drugs, covering 56 different drug classes. The systematic review was limited to studies using acute, systemic drug administration in naive animals. Results: Qualitative data synthesis showed that most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments, reduced fear potentiation in 29% of the experiments, and were without effect in 29% of the experiments. Meta-analyses could be performed for five drug classes and showed that benzodiazepines, buspirone, 5-HT1A agonists, 5-HT1A antagonists, and mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle response, which may reflect contextual anxiety, was only significantly reduced by benzodiazepines and 5-HT1A antagonists. No associations were found between drug effects and methodological characteristics, except for strain. Conclusions: The fear-potentiated startle test appears to have moderate to high predictive validity and may serve as a valuable tool for the development of novel anxiolytics. Given the limited available data, the generally low study quality and high heterogeneity additional studies are warranted to corroborate the findings of this review. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is a chemotherapeutic agent widely used to treat a variety of tumors. Nonetheless, MTX‐induced hippocampal neurotoxicity is a well‐defined dose‐limiting adverse effect that limits clinical utility. Proinflammatory cytokine production and oxidative stress are possible mechanisms for MTX‐induced neurotoxicity. Buspirone (BSP), a partial agonist of the 5‐HT1a receptor (5‐HT1aR), has emerged as an anxiolytic drug. BSP has been shown to possess antioxidant and anti‐inflammatory effects. The current study investigated BSP's potential anti‐inflammatory and antioxidant effects in attenuating MTX‐induced hippocampal toxicity. Rats received either BSP (1.5 mg/kg) orally for 10 days and MTX (20 mg/kg) i.p. on Day 5. BSP administration markedly protected hippocampal neurons from drastic degenerated neuronal changes induced by MTX. BSP significantly attenuated oxidative injury by downregulating Kelch‐like ECH‐associated protein 1 expression while potently elevating hippocampal Nrf2, heme oxygenase‐1, and peroxisome proliferator‐activated receptor expression. BSP dampened inflammation by reducing NO2−, tumor necrosis factor‐alpha, IL‐6, and interleukin 1 beta levels mediated by downregulating NF‐κB and neuronal nitric oxides synthase expression. Moreover, BSP potently counteracted hippocampal pyroptosis by downregulating NLRP3, ASC, and cleaved‐caspase‐1 proteins. Therefore, BSP may represent a promising approach to attenuate neurotoxicity in patients receiving MTX. [ABSTRACT FROM AUTHOR]