Anxiolytic Drugs Research Articles

Detecting drugs in dry bone: a pilot study of skeletal remains with a post-mortem interval over 23 years

In decomposed or skeletonized bodies, conventional matrices used in forensic toxicology may no longer be available for analysis. The aim of this paper was to test the survival and detection of toxicological substances in dry bone samples with over 23 years of post-mortem interval. In this perspective, bone samples from the cranium, ribs, and vertebrae of seven skeletons from the CAL Milano Cemetery Skeletal Collection, buried for over 23 years, fully decomposed and altered by taphonomic factors were selected based on their ante-mortem data, which included verified or suspected drug addictions or overdose. Qualitative and quantitative analyses were performed with Dionex™ ASE™ 350 Accelerated Solvent Extractor and Q-Exactive Orbitrap-mass spectrometry with a HPLC system. Positive results were obtained in six of the seven cases, and different psychoactive drugs (and in some cases their active metabolites) were detected, including analgesic (two opioids: methadone and buprenorphine) and anxiolytic drugs (benzodiazepines, in particular delorazepam, diazepam, nordiazepam, and lorazepam), a cannabinoid metabolite (THCCOOH) as well as metabolites of stimulants (benzoylecgonine and MDA). Consequently, this research shows that toxicological substances may be found in bone tissue after over 23 years of post-mortem interval.

Psychiatric manifestations of anti-N-methyl-D-aspartate receptor encephalitis: A case report.

Psychiatric manifestations of anti-N-methyl-D-aspartate receptor encephalitis: A case report.

Termiticidal Activity of Ethanolic and n- Hexane Leaf Extraction of Calotropis procera, Cannabis indica and Mentha longifolia Against a Higher Termite Microtomes obesi

Depression is considered as affective disorder characterized by change in mood, lack of interest in the surrounding. It is one of the mental health problems of people all over the world. Depression is a multifaceted condition characterised by episodes of mood disturbances alongside other symptoms such as anhedonia, psychomotor complaints, feelings of guilt and suicidal tendencies, all of which can range in severity. Anxiety and fear can be defined as response of subject to real or potential threats that may impair his/her homeostasis that can significantly mark function and quality of life. Some of depressive disorder overlap those of anxiety disorders, including severe phobias, generalized anxiety disorder, social anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder. Anxietyrelated disorders such as patient’s nervousness, obsessive compulsive disorder and post-traumatic stress are foremost causes of infirmity in the world. Antidepressant and anxiolytic drug are the drug use for treatment of depression and anxiety but there are several side effect of these drug were observed like dry mouth, mental confusion, weakness and sedation. So, we evaluate the anti-depressant and anti-anxiety effect of N. Jatamansi root extract in rats by dose dependent manner. The behavior assessment observed by force swim test, locomotor activity, tail suspension test and elevated plus maze for depression and anxiety experimentation. The drug given 150 mg/kg and 300 mg/kg by oral route. The study observed that the ethanolic root extract reduced depression and anxiety generated by force swim test, tail suspension method, actophotometer and elevated plus maze.

Delirium risk factors analysis post proximal femur fracture surgery in elderly.

Background and aim:The increase in the average-age and in the percentage of elderly people implies an exponential increase in fractures of the proximal femur. A common consequence of hip fracture in elderly patients is delirium, characterized by cognitive confusion or a lethargic-type condition. Predisposing factors have been identified, but risk factors assessment useful for managing clinical intervention, has not received unanimous consent. This work aims to identify the potential risk factors for delirium in the elderly operated for hip fracture.Methods:In this prospective observational study, we included 83 patients aged >65 years. Patients undergoing osteosynthesis of the femur and hip replacement for fractures were included. Patients already delusional in the pre-operative period were excluded. At the time, deadlines T0 (pre-operative), and T1,T3,T7 post-operative day, delirium, hematic parameters, blood transfusions, were assessed.Results:Level of delirium was assessed obtaining 80% not delusional and 20% delusional. Glycemia and hemoglobin were not found to be risk factors, although they are known to influence cognitive status; we hypothesize they should be considered predisposing factors. Comorbidities such as atrial fibrillation and Chronic Obstructive Pulmonary Disease were found associated with delirium. The most advanced age, anxiolytic drugs, the use of benzodiazepine as anaesthetic, the time surgical waiting, were found significantly associated with delirium.Conclusions:Taken together, findings of this prospective observational study showed that environmental and metabolic risk factors might contribute to make elderly susceptible to develop postoperative delirium following hip surgery. Thus, these patients should be adequately assessed and monitored. (www.actabiomedica.it)

Higher prescription of antidepressants and/or anxiolytics among chronic obstructive pulmonary disease patients.

Background:Chronic obstructive pulmonary disease (COPD) is often accompanied by psychiatric problems, such as depression and anxiety, affecting both treatment outcomes and mortality. Evidence for the number of COPD patients using medication for these disorders is sparse. In this study, chronic antidepressant (ATD) and anxiolytic (ANX) drug use – to identify depression and anxiety – among COPD patients was compared with subjects with or without other chronic diseases.Methods:The NControl database containing prescription data of 800 pharmacies including 7 million individuals in The Netherlands was used. Patients of age 55+ years who received frequent prescriptions – at least two/year in 5 out of 6 years – for COPD medication, dermatological drugs, disease-modifying antirheumatic drugs (DMARDs), statins and oral glucose-lowering medication were analyzed for concomitant chronic use of ATDs and ANXs between 1 January 2013 and 1 January 2019. All other subjects aged 55+ years were included as a control group (control group 1). This group was further stratified into a group of subjects that received frequent prescriptions of any kind (control group 2).Results:15.2% of the patients that receive COPD treatment (n = 96,319), 15.3% of subjects that are treated for dermatological problems (n = 62,865), 13.2% of subjects that receive DMARDs (n = 7900), 11.6% of statins users (n = 422,376) and 11.4% of oral glucose-lowering medication users (n = 165,975) are also chronically treated for depression or anxiety, compared with 2.6% (control group 1; n = 3,290,608) and 11.4% (control group 2; n = 757,947). In general, female and 75+ years aged subjects showed a higher risk for using ATDs and ANXs chronically. In the COPD and the dermatological patient group the risk was the highest compared with the other patient groups.Conclusions:The rates of chronic ATD and ANX use and the risk of having depression and/or anxiety are especially high in COPD patients, indicating that psychiatric problems are more common in COPD than in most other chronic diseases. In general, age and gender strongly influence the risk of chronically using ATDs and ANXs. The reviews of this paper are available via the supplemental material section.

Jie-Yu-He-Huan Capsule Ameliorates Anxiety-Like Behaviours in Rats Exposed to Chronic Restraint Stress via the cAMP/PKA/CREB/BDNF Signalling Pathway.

Chronic stress is a critical factor in the aetiology of anxiety disorders; however, in the clinic, enduring and preventive measures are not available, and therapeutic drugs are associated with inevitable side effects. Our study established an anxiety rat model using chronic restraint stress (CRS) and assessed these animals using the open-field test, elevated plus-maze test, and light-dark box test. Jie-Yu-He-Huan capsule (JYHH), a Chinese medicine formula, was used as a preventative drug. The HPA axis-mediated release of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone from the hypothalamus was tested. In the hippocampus and prefrontal cortex, concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid, as well as monoamine oxidase A, glucocorticoid receptor, and 5-HT1A receptor expression levels, were measured. Furthermore, we examined protein and mRNA expression of cAMP-PKA-CREB-BDNF pathway components. The results showed that JYHH had a significant preventative effect on the anxiety-like behaviour induced by CRS and prevented abnormal changes in the HPA axis and 5-HT system. Furthermore, CRS inhibited the cAMP-PKA-CREB-BDNF pathway, which returned to normal levels following JYHH treatment. This might be the underlying molecular mechanism of the antianxiety effect of JYHH, which could provide a new clinical target for preventative anxiolytic drugs for chronic stress.

Сучасні аспекти застосування психофармакотерапії у хворих на поширений псоріаз

The objective: to optimize the treatment of patients with advanced psoriasis by applying a complex method that includes psychopharmacotherapy. Materials and methods. There were 163 patients with acute psoriasis aged 18 to 74 years, of which 88 were men (53.9%) and 74 were women (46.1%). All patients underwent a comprehensive clinical and laboratory examination in accordance with the guidelines. To determine the psychoemotional state, all patients with psoriasis were subjected to a pathopsychological examination: determination of the level of reactive anxiety (RA) on the Spielberger-Hanin scale. Patients with moderate to high levels of anxiety disorders were divided into two groups. The first therapeutic group (I Group, 74 people) consisted of patients who received the anxiolytic drug mebicar against the background of traditional therapy. The therapeutic comparison group (Group II, 72 people) was formed by patients who received only traditional therapy. Results. It was found that the average RT score among all patients was (50.9 ± 0.8), which corresponded to a high level. The majority of patients (85–52.2%) had high RA levels. At the end of the course of therapy with the developed method, patients of Group I had a statistically significant decrease in the level of RA by 1.4 times and a decrease in the average score to (35.2 ± 0.4) points. But in patients of Group II, the RA level also decreased, but only by 1.1 times (p < 0.05) and the average score was significantly higher compared to the indicator in Group I by 1.3 times. Patients in Group I had an improvement in the clinical manifestations of psoriasis (PASI50) on average (10.3 ± 0.1) days of treatment. A similar result was achieved in patients of Group II only on (15.5 ± 0.2) days, which is significantly later than in Group I. Consequently, the appointment of differentiated psychopharmacotherapy contributed to an earlier regression of clinical manifestations. Conclusions. It was found that the vast majority of patients with psoriasis had a high level of RA, which should be taken into account when prescribing complex therapy. The appointment of psychopharmacotherapy contributed to the normalization of the psychoemotional state and earlier regression of clinical manifestations (the PASI50 state was achieved on (10.3 ± 0.1) days of treatment, which is 5.2 days less than in patients who received only traditional therapy).

Involvement of GABAergic and nitrergic systems in the anxiolytic and hypnotic effects of Curcuma longa: its interaction with anxiolytic-hypnotics

Abstract Objectives Concurrent use of herbs with drugs have become a major healthcare problem. Herb-drug interactions could lead to therapeutic failure or toxicity. Hence, this study seeks to evaluate the impact of combining Curcuma longa rhizome (CL) with selected anxiolytic and hypnotic drugs. Methods CL (100, 200 or 400 mg/kg, p.o.) was administered to mice 1 h before subjecting the animals to elevated plus maze (EPM), hole board test (HBT), open field test (OFT) and rotarod test for anxiolytic-like effect as well as hexobarbitone-induced sleeping time (HIST) for hypnotic activity. The involvement of GABAergic and nitrergic systems in CL-induced anxiolytic and hypnotic actions were also evaluated. The effect of concurrent use of CL with midazolam, imipramine, nifedipine, propranolol and carbamazepine were evaluated in anxiolytic-hypnosis models. Results The peak anxiolytic-like effect of CL was obtained at 400 mg/kg in the EPM and hole-board test without affecting muscle coordination in the rotarod test while the peak hypnosis-potentiation was observed at 100 mg/kg. CL-induced anxiolytic-hypnotic-like effects were reversed by the pretreatment of mice with flumazenil or NG-nitro-l-arginine. Conclusions Curcuma longa possesses anxiolytic and hypnotic effects through its interaction with GABAergic and nitrergic systems. Conversely, co-administration of C. longa with midazolam potentiate barbiturate-induced hypnosis.

Involvement of GABAergic and nitrergic systems in the anxiolytic and hypnotic effects of Curcuma longa: its interaction with anxiolytic-hypnotics.

Concurrent use of herbs with drugs have become a major healthcare problem. Herb-drug interactions could lead to therapeutic failure or toxicity. Hence, this study seeks to evaluate the impact of combining Curcuma longa rhizome (CL) with selected anxiolytic and hypnotic drugs. CL (100, 200 or 400mg/kg, p.o.) was administered to mice 1h before subjecting the animals to elevated plus maze (EPM), hole board test (HBT), open field test (OFT) and rotarod test for anxiolytic-like effect as well as hexobarbitone-induced sleeping time (HIST) for hypnotic activity. The involvement of GABAergic and nitrergic systems in CL-induced anxiolytic and hypnotic actions were also evaluated. The effect of concurrent use of CL with midazolam, imipramine, nifedipine, propranolol and carbamazepine were evaluated in anxiolytic-hypnosis models. The peak anxiolytic-like effect of CL was obtained at 400mg/kg in the EPM and hole-board test without affecting muscle coordination in the rotarod test while the peak hypnosis-potentiation was observed at 100mg/kg. CL-induced anxiolytic-hypnotic-like effects were reversed by the pretreatment of mice with flumazenil or NG-nitro-l-arginine. Curcuma longa possesses anxiolytic and hypnotic effects through its interaction with GABAergic and nitrergic systems. Conversely, co-administration of C.longa with midazolam potentiate barbiturate-induced hypnosis.

Современные тенденции в лечении хронического рецидивирующего бактериального цистита

INTRODUCTION Every year, more than 7 million women go to the doctor for chronic cystitis. An important factor is the psychoemotional component of this disease. OBJECTIVE comparative analysis of various options for complex treatment of women with chronic recurrent bacterial cystitis using phototherapy, chronotherapy and correction of psychoemotional disorders with the anxiolytic drug Adaptol. MATERIALS AND METHODS 90 women with chronic recurrent bacterial cystitis in the acute stage were examined and divided into 3 groups of 30 people. In group 1, patients received basic therapy with Furamag (furazidin kalium). In group 2, patients received standard therapy in combination with phototherapy in the acrophase of the chronorhythm. In group 3, basic therapy was performed in combination with phototherapy in the acrophase of the chronorhythm and Adaptol. The severity of dysuria and pain, leukocyturia, bacteriuria, chronobiological and psychoemotional status were evaluated. RESULTS Initially, all patients showed signs of desynchronosis and psychoemotional disorders. All groups showed signs of exacerbation of chronic cystitis. The results obtained on the 5th day of therapy in groups 2 and 3 were statistically significantly different (p<0.05) from those in group 1. In group 3, the number of nocturnal urination (0.9+/-0.7), the number of imperative urges per day (0.7+/-0.5), and the intensity of pain (0.7+/-0.6) were the closest to normal. By day 10, clinical and laboratory parameters in all three groups reached normal values, which indicates the effectiveness of the therapy in each of the groups. CONCLUSION Thus, the use of Furamag and Adaptol in combination with phototherapy at the maximum peaks of psychoemotional and physiological activity of the body effectively stops the clinical and laboratory manifestations of the disease, corrects the mental status and improves the quality of life of women in a shorter period of treatment.

Attenuation of Anxiety-Like Behavior by Helichrysum stoechas (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons.

The long-term use of anxiolytic and antidepressant drugs can cause a plethora of side effects and the use of complementary and alternative medicine, which is generally considered safer than conventional medicine, is consistently increasing. Helichrysum stoechas (L.) Moench methanolic extract (HSE) has shown MAO-A inhibitory properties in previous studies. With the aim of obtaining innovative and safer therapies for mood disorders, this study investigated the potential activity of HSE in the management of anxiety- and depression-related symptoms. HSE showed dose-dependent (30–100 mg/kg p.o.) anxiolytic-like activity in the light dark box and marble burying tests, without any antidepressant-like activity, as shown by the results of the tail suspension test. Additionally, HSE did not have any effect on the modulation of pain, which highlights its selectivity in the control of anxiety-related behavior. At active doses, HSE did not produce any sedative effect or result in impaired motor coordination and memory functions. Western blotting experiments showed the ability of HSE to counteract the reduction in the phosphorylation of ERK44/42, to restore brain-derived neurotrophic factor (BDNF) expression and to return cyclic AMP response element binding (CREB) levels to basal levels in noradrenergic hippocampal neurons of mice exposed to an anxiety-related environment, which indicates a protective role against anxiety behavior. These results suggest that oral administration of HSE might represent an interesting opportunity for the management of anxiety disorders.

Pharmacological characterisation of anticonvulsant effects elicited by erythrartine.

The erythrinan alkaloids erythravine and 11α-hydroxy-erythravine from Erythrina verna (Vell.) have been extensively investigated for their anxiolytic and anticonvulsant effects. Both are structurally similar to the erythrartine that also exhibit anxiolytic effects, but there is no report on its anticonvulsant potential. Since some anxiolytic drugs can be useful in the management of epileptic seizures, we investigated whether erythrartine could prevent seizures induced by different chemoconvulsants. Experiments were performed using different concentrations of erythrartine injected via intracerebroventricular in rats submitted to pilocarpine, kainic acid, pentylenetetrazol or picrotoxin-induced seizures. Moreover, the rotarod test was performed to verify the effects of erythrartine on animal motor coordination. Our data showed for the first time that erythrartine prevented the occurrence of seizures induced by all of the chemoconvulsants tested and did not affect locomotor performance neither produced sedative effect on animals. Obtained results validate the ethnopharmacological significance of E. verna and provide new information on erythrartine, another erythrinian alkaloid of biotechnological and medicinal interest.

Comorbidities of alopecia areata: a population-based cohort study.

Previous studies have associated alopecia areata (AA) with a number of comorbidities. However, the timing between AA and the development of such comorbidities remains poorly understood. To examine the temporal relationship between AA diagnosis and comorbidity development in Denmark. A Danish nationwide register-based cohort study was performed on all individuals diagnosed with AA between 2007 and 2016 (n=1843), and each patient was matched for age and sex with 10 healthy controls (HCs). Time between AA and comorbidity development was assessed, and incidence rate ratios (IRRs) were calculated to assess risk of comorbidity following initial AA diagnosis. Use of antidepressant and anxiolytic drugs were mostly started prior to AA diagnosis, and these drugs were used more frequently before than after diagnosis with AA. Additional frequent comorbidities included thyroid disease, hyperlipidaemia, type 2 diabetes and asthma. Most comorbidities occurred prior to AA diagnosis; however, among those that occurred after AA diagnosis, antidepressants (IRR=1.26, 95% CI 1.01-1.56), anxiolytics (IRR=1.55, 95% CI 1.17-2.05), atopic dermatitis (AD; IRR=9.41, 95% CI 4.00-22.16), asthma (IRR=2.17, 95% CI 1.46-3.21), vitiligo (IRR=30.35, 95% CI 6.13-150.39), Crohn disease (CD; IRR=3.04; 95% CI 1.22-7.56) and thyroid disease (IRR=2.38; 95% CI 1.72-3.29) occurred more frequently among patients with AA compared with controls. A diagnosis of AA was significantly associated with risk of several comorbidities, most notably vitiligo, AD and CD. Nonetheless, the majority of patients appeared to have developed these comorbidities prior to AA diagnosis, suggesting that a thorough medical history screening by dermatologists at the initial visit may be appropriate.

Abstract PO-047: Lorazepam modifies the pancreatic ductal adenocarcinoma tumor microenvironment

Abstract The aim of this work was to determine the role of the benzodiazepine (BZD) lorazepam, an anxiolytic drug, in modifying the pancreatic ductal adenocarcinoma (PDA) tumor microenvironment. PDA is a lethal malignancy. Poor survival rates and tumor intrinsic aspects of the disease, such as altered cytokine pools, promote significant levels of anxiety in patients. Approximately 25% of PDA patients will be prescribed BZDs. Epidemiological evidence suggests BZDs increase the risk of cancer development, but no group has determined the impact of BZDs on the PDA tumor microenvironment. Recent research has established that BZDs promote the signaling of GPR68, a proton-sensing G protein-coupled receptor activated by the acidic tumor microenvironment. GPR68 is expressed on PDA cancer-associated fibroblasts (CAFs) and promotes pro-inflammatory and pro-fibrotic signaling. Additionally, we performed covariate adjusted analyses of pancreatic cancer patients who received chemotherapy at Roswell Park from 2004 to 2020. Patients receiving lorazepam (LOR), an n-unsubstituted BZD that strongly activates GPR68, had shorter progression-free survival (PFS) relative to non-users (HR 3.83 (1.53, 9.57). In contrast, patients receiving alprazolam (ALP), an n-substituted BZD and GPR68 non-activator, had improved PFS relative to non-users (HR 0.38 (0.16-0.92). It is essential that we determine the impact of BZDs and GPR68 activation on the PDA tumor microenvironment and therapeutic response. We hypothesize that BZDs which are strong GPR68 activators will stimulate fibrosis and inflammatory signaling, promoting a more desmoplastic tumor microenvironment, decreasing the efficacy of chemotherapy. Using a subcutaneous KPC allograft mouse model, we found that lorazepam, a strong GPR68-activating BZD, modified the tumor microenvironment by increasing α-SMA (smooth muscle actin) expression, collagen deposition, and ischemic necrosis. Similarly, under acidic conditions, lorazepam-treated primary mouse and human CAFs promoted the mRNA expression of α-SMA and the pro-inflammatory cytokine, interleukin-6. Overall, this research indicates that lorazepam treatment significantly impacts the PDA tumor microenvironment. Significance: This research may guide the development of new clinical recommendations for prescribing anxiolytic drugs to PDA patients. The results of this research will likely be applicable to other cancer types which are reliant on CAFs for growth, such as colon cancer. Citation Format: Abigail C. Cornwell, Abdulrahman A. Alahmari, Arwen A. Tisdale, Michael E. Feigin. Lorazepam modifies the pancreatic ductal adenocarcinoma tumor microenvironment [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-047.

Uso da Passiflora incarnata L. no tratamento alternativo do transtorno de ansiedade generalizada

O presente estudo trata-se de uma pesquisa bibliográfica, qualitativa e descritiva da importância do uso da Passiflora incarnata como fitofármaco utilizado na busca de uma alternativa viável e mais acessível, buscando contribuir para o tratamento alternativo do transtorno de ansiedade generalizado. Neste sentido, é bom esclarecer a terminologia “ansiedade” que é então descrita como um estado emocional presente em diversos momentos da vida, bem como, na correria do dia-a-dia. Os sintomas se manifestam através de pensamentos pessimistas, aflições, angústia e em momentos de perturbações, como o que estamos passando com a pandemia de COVID-19 e seus perigos de infecção, doença e falta de informação concisa. Inúmeras drogas sintéticas como os benzodiazepínicos são utilizadas no tratamento dos sintomas e no controle das manifestações traumáticas que a ansiedade carrega. No entanto, o uso contínuo de drogas sintéticas ansiolíticas dentre outras, acarretam desgaste emocional, estresse diário e dependência ocasionando sempre doses maiores. Outro sério problema é a associação destas com outras drogas farmacêuticas, bem mesmo, a ingestão de bebidas alcoólicas, provocando irritabilidade, descontrole mental, coma e óbito. Uma possível sugestão alternativa e segura é o uso de fitofármacos como a Passiflora incarnata, que em inúmeros estudos apresentam como uma eficiênte opção para o tratamento da ansiedade, devido aos bons resultados no controle sintomatológico e na associação conjunta entre outras drogas vegetais e sintéticas.

“Pode gritar, ninguém vai acreditar em você”: A saúde mental de mulheres vítimas de violência sexual

O estudo tem como objetivo descrever as consequências à saúde mental da mulher vítima de violência sexual, tracejando os cuidados recebidos nos serviços da Rede de Atenção à Saúde. Trata-se de uma revisão integrativa de literatura, com abordagem qualitativa, realizada por meio da buscativa de artigos indexados na Biblioteca Virtual em Saúde (BVS), com o auxílio das seguintes bases de dados: Scientific Electronic Library Online (SCIELO), National Center for Biotechnology Information (PUBMED), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Base de Dados de Enfermagem (BDENF), e Periódicos Eletrônicos em Psicologia (PEPSIC). Os critérios de inclusão compreendem pesquisas de revisão da literatura disponíveis nos bancos de dados descritos, compreendidos entre os anos de 2005 a 2020. Como critérios de exclusão, não foram considerados artigos mediante a recompensação monetária, incompletos e não convergentes com este estudo. Para o levantamento dos dados foram analisados 13 artigos e 03 estudos referentes à entidades de saúde. Os resultados constatam a necessidade do acompanhamento especializado à saúde mental das mulheres vítimas de violência sexual, visto a drástica mudança comportamental após o ato de violência. Consequentemente, resultando em depressão, ansiedade, uso de medicamentos ansiolíticos, traumas, medo, isolamento social, uso de álcool e drogas, preocupação, insônia, ataques de pânico, suicídio, entre outros fatores. O estudo identificou a importância da percepção dos profissionais de saúde, para a identificação dos casos imediatos, visando promover práticas assistenciais de acolhimento, e uma percepção qualificada para atender essa demanda, viabilizando o acolhimento inicial, acompanhamento integral, assistencial e humanizado.

Silexan does not affect driving performance after single and multiple dose applications: Results from a double-blind, placebo and reference-controlled study in healthy volunteers

Anxiolytic drugs often have sedative effects that impair the ability to drive. Our double-blind, randomized crossover trial investigated the effect of Silexan, a non-sedating, anxiolytic herbal medicinal product, on driving performance in healthy volunteers. Part 1 aimed at demonstrating equivalence between 80 mg/d Silexan and placebo. Part 2 was performed to demonstrate superiority of 160 and 320 mg Silexan over 1 mg lorazepam and included a placebo arm for assay sensitivity. Driving performance was assessed in a validated, alcohol-calibrated simulator test. The primary outcome was the standard deviation of the lane position (SDLP). Secondary outcomes included driving errors and sleepiness. Fifty and 25 subjects were randomized in Parts 1 and 2, respectively. In Part 1, Silexan 80 mg was confirmed to be equivalent to placebo after single administration (equivalence range: δ = ±2 cm). The 95% confidence interval (CI) for the SDLP marginal mean value difference Silexan–placebo for single administration was −1.43; +1.38 and thus similar to the 95% CI of −1.45; +0.79 cm for 7 days’ multiple dosing. In Part 2, 95% CIs for SDLP marginal mean value differences to lorazepam were −8.58; −5.42 cm for Silexan 160 mg and −8.65; −5.45 cm for 320 mg (p < 0.001). Confirmatory results were supported by secondary outcomes, where results for Silexan were comparable to placebo and more favorable than for lorazepam. The study demonstrates that single doses of up to 320 mg Silexan and multiple doses of 80 mg/d have no adverse effect on driving performance.

The New Dipeptide TSPO Ligands: Design, Synthesis and Structure-Anxiolytic Activity Relationship.

The translocator protein (TSPO, 18 kDa) plays an important role in the synthesis of neurosteroids by promoting the transport of cholesterol from the outer to the inner mitochondrial membrane, which is the rate-limiting step in neurosteroidogenesis. Stimulation of TSPO by appropriate ligands increases the level of neurosteroids. The present study describes the design, synthesis and investigation of anxiolytic-like effects of a series of N-acyl-tryptophanyl-containing dipeptides. These novel dipeptide TSPO ligands were designed with the original drug-based peptide design strategy using alpidem as non-peptide prototype. The anxiolytic activities were investigated in Balb/C mice using the illuminated open-field and elevated plus-maze tests in outbred laboratory mice ICR (CD-1). Dipeptide GD-102 (N-phenylpropionyl-l-tryptophanyl-l-leucine amide) in the dose range of 0.01–0.5 mg/kg intraperitoneally (i.p.) has a pronounced anxiolytic activity. The anxiolytic effect of GD-102 was abolished by PK11195, a specific TSPO antagonist. The structure–activity relationship study made it possible to identify a pharmacophore fragment for the dipeptide TSPO ligand. It was shown that l,d-diastereomer of GD-102 has no activity, and the d,l-isomer has less pronounced activity. The anxiolytic activity also disappears by replacing the C-amide group with the methyl ester, a free carboxyl group or methylamide. Consecutive replacement of each amino acid residue with glycine showed the importance of each of the amino acid residues in the structure of the ligand. The most active and technologically available compound GD-102, was selected for evaluation as a potential anxiolytic drug.

Development of a Method for Determination of Related Impurities in GML-3 Drug Substance: A New Compound with Anxiolytic Properties

A method for determination of related impurities in the new anxiolytic drug substance GML-3 was developed. HPLC and TLC techniques that could identify starting materials and synthetic intermediates and quantify them and unidentified impurities with contents of 0.05% and less in the drug substance were developed. The proposed techniques could be used further for quality control of GML-3 drug substance.

A Comparison of Hematological, Immunological, and Stress Responses to Capture and Transport in Wild White Rhinoceros Bulls (Ceratotherium simum simum) Supplemented With Azaperone or Midazolam.

Capture and transport are essential procedures for the management and conservation of southern white rhinoceroses (Ceratotherium simum simum), but are associated with stress-induced morbidity and mortality. To improve conservation efforts, it is crucial to understand the pathophysiology of rhinoceros stress responses and investigate drug combinations that could reduce these responses. In this study we measured rhinoceros stress responses to capture and transport by quantifying hematological and immunological changes together with adrenal hormone concentrations. We investigated whether the potent anxiolytic drug midazolam was able to mitigate these responses compared to azaperone, which is more commonly used during rhinoceros transport. Twenty three wild white rhinoceros bulls were transported for 6 h (280 km) within the Kruger National Park for reasons unrelated to this study. Rhinoceroses were immobilized with either etorphine-azaperone (group A, n = 11) or etorphine-midazolam (group M, n = 12) intramuscularly by darting from a helicopter. Azaperone (group A) or midazolam (group M) were re-administered intramuscularly every 2 h during transport. Serial blood samples were collected at capture (TC), the start of transport (T0) and after 6 h of transport (T6). Changes in hematological and immunological variables over time and between groups were compared using general mixed models. Increases in plasma epinephrine and serum cortisol concentrations indicated that rhinoceroses mounted a stress response to capture and transport. Packed cell volume decreased from TC to T6 indicating that stress hemoconcentration occurred at TC. Neutrophils progressively increased and lymphocytes and eosinophils progressively decreased from T0 to T6, resulting in an increase in neutrophil to lymphocyte ratio; a characteristic leukocyte response to circulating glucocorticoids. A reduction in serum iron concentrations may suggest the mounting of an acute phase response. Rhinoceroses experienced a decrease in unsaturated fatty acids and an increase in lipid peroxidation products at capture and toward the end of transport indicating oxidative stress. Midazolam, at the dose used in this study, was not able to mitigate adrenal responses to stress and appeared to directly influence leukocyte responses.