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1.
Cell ; 184(5): 1362-1376.e18, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33545087

ABSTRACT

Lungfishes are the closest extant relatives of tetrapods and preserve ancestral traits linked with the water-to-land transition. However, their huge genome sizes have hindered understanding of this key transition in evolution. Here, we report a 40-Gb chromosome-level assembly of the African lungfish (Protopterus annectens) genome, which is the largest genome assembly ever reported and has a contig and chromosome N50 of 1.60 Mb and 2.81 Gb, respectively. The large size of the lungfish genome is due mainly to retrotransposons. Genes with ultra-long length show similar expression levels to other genes, indicating that lungfishes have evolved high transcription efficacy to keep gene expression balanced. Together with transcriptome and experimental data, we identified potential genes and regulatory elements related to such terrestrial adaptation traits as pulmonary surfactant, anxiolytic ability, pentadactyl limbs, and pharyngeal remodeling. Our results provide insights and key resources for understanding the evolutionary pathway leading from fishes to humans.


Subject(s)
Adaptation, Biological , Biological Evolution , Fishes/genetics , Whole Genome Sequencing , Animal Fins/anatomy & histology , Animal Fins/physiology , Animals , Extremities/anatomy & histology , Extremities/physiology , Fishes/anatomy & histology , Fishes/classification , Fishes/physiology , Phylogeny , Respiratory Physiological Phenomena , Respiratory System/anatomy & histology , Vertebrates/genetics
2.
Biol Pharm Bull ; 47(1): 328-333, 2024.
Article in English | MEDLINE | ID: mdl-38296462

ABSTRACT

Alzheimer's disease (AD) is accompanied by behavioral and psychological symptoms of dementia (BPSD), which is often alleviated by treatment with psychotropic drugs, such as antidepressants, hypnotics, and anxiolytics. If these drugs also inhibit acetylcholinesterase (AChE) activity, they may contribute to the suppression of AD progression by increasing brain acetylcholine concentrations. We tested the potential inhibitory effects of 31 antidepressants, 21 hypnotics, and 12 anxiolytics on recombinant human AChE (rhAChE) activity. At a concentration of 10-4 M, 22 antidepressants, 19 hypnotics, and 11 anxiolytics inhibited rhAChE activity by <20%, whereas nine antidepressants (clomipramine, amoxapine, setiptiline, nefazodone, paroxetine, sertraline, citalopram, escitalopram, and mirtazapine), two hypnotics (triazolam and brotizolam), and one anxiolytic (buspirone) inhibited rhAChE activity by ≥20%. Brotizolam (≥10-6 M) exhibited stronger inhibition of rhAChE activity than the other drugs, with its pIC50 value being 4.57 ± 0.02. The pIC50 values of the other drugs were <4, and they showed inhibitory activities toward rhAChE at the following concentrations: ≥3 × 10-6 M (sertraline and buspirone), ≥10-5 M (amoxapine, nefazodone, paroxetine, citalopram, escitalopram, mirtazapine, and triazolam), and ≥3 × 10-5 M (clomipramine and setiptiline). Among these drugs, only nefazodone inhibited rhAChE activity within the blood concentration range achievable at clinical doses. Therefore, nefazodone may not only improve the depressive symptoms of BPSD through its antidepressant actions but also slow the progression of cognitive symptoms of AD through its AChE inhibitory actions.


Subject(s)
Amoxapine , Anti-Anxiety Agents , Triazolam , Humans , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/therapeutic use , Acetylcholinesterase , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/therapeutic use , Sertraline , Clomipramine , Mirtazapine , Paroxetine , Citalopram , Escitalopram , Buspirone , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use
3.
Mol Divers ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758508

ABSTRACT

In the contemporary landscape, anxiety and seizures stand as major areas of concern, prompting researchers to explore potential drugs against them. While numerous drugs have shown the potential to treat these two neurological conditions, certain adverse effects emphasize the need for development of safer alternatives. This study seeks to employ an in silico approach to evaluate natural compounds, particularly curcumins, as potential inhibitors of GABA-AT to mitigate anxiety and seizures. The proposed methodology includes generating a compound library, minimizing energy, conducting molecular docking using AutoDock, molecular dynamics simulations using Amber, and MM-GBSA calculations. Remarkably, CMPD50 and CMPD88 exhibited promising binding affinities of - 9.0 kcal/mol and - 9.1 kcal/mol with chains A and C of GABA-AT, respectively. Further, MM-GBSA calculations revealed binding free energies of - 10.88 kcal/mol and - 10.72 kcal/mol in CMPD50 and CMPD88, respectively. ADME analysis showed that these compounds contain drug-likeness properties and might be considered as potential drug candidates. The findings from this study will have practical applications in the field of drug discovery for the development of safer and effective drugs for treatment of anxiety and seizures. Overall, this study will lay the groundwork for providing valuable insights into the potential therapeutic effects of curcumins in alleviating anxiety and seizures, establishing a computational framework for future experimental validation.

4.
Arch Womens Ment Health ; 27(4): 619-623, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38376615

ABSTRACT

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.


Subject(s)
Anti-Anxiety Agents , Breast Feeding , Buspirone , Lactation , Milk, Human , Humans , Milk, Human/chemistry , Milk, Human/metabolism , Female , Adult , Anti-Anxiety Agents/analysis , Anxiety/drug therapy , Infant , Infant, Newborn , Chromatography, Liquid
5.
Aust N Z J Psychiatry ; 58(10): 914-917, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39129192

ABSTRACT

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.


Subject(s)
Psychotropic Drugs , Humans , Australia , Male , Female , Adult , Aged , Middle Aged , Adolescent , Psychotropic Drugs/therapeutic use , Young Adult , Child , Aged, 80 and over , Child, Preschool , Infant , Infant, Newborn , Age Factors , Drug Prescriptions/statistics & numerical data , Sex Factors
6.
Metab Brain Dis ; 39(5): 731-739, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38720093

ABSTRACT

Brain function is highly altered by glucose toxicity related to diabetes. High consumption of sugar in normal conditions is suspected to affect as well brain integrity. The present study investigates the possible effects of short-term exposure to high sugar diet on brain redox homeostasis in healthy mice. Male adult healthy mice were divided into two groups: control (CG) and sugar-exposed group (SG), that was exposed continually to 10% of glucose in drinking water for 7 days and 20% sucrose pellets food. Behavior, blood glucose variability and cerebral cortex oxidative stress biomarkers were measured at the end of exposure. Animals exposed to the high sugar diet expressed a significant increase in blood glucose levels and high glucose variability compared to control. These animals expressed as well anxiolytic behavior as revealed by the plus maze test. Exposure to the sugar diet altered redox homeostasis in the brain cortex as revealed by an increase in lipid peroxidation and the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione-s-transferase (GST). On the other hand, catalase (CAT) activity was decreased, and reduced glutathione (GSH) level was not altered compared to control. Further studies are required to understand the mechanisms trigging oxidative stress (OS) in the brain in response to short term exposure to high sugar diet and glucose fluctuations.


Subject(s)
Blood Glucose , Cerebral Cortex , Oxidative Stress , Animals , Oxidative Stress/drug effects , Cerebral Cortex/metabolism , Cerebral Cortex/drug effects , Male , Mice , Blood Glucose/metabolism , Lipid Peroxidation/drug effects , Anxiety/metabolism , Anti-Anxiety Agents/pharmacology , Catalase/metabolism , Glutathione/metabolism , Superoxide Dismutase/metabolism , Glucose/metabolism
7.
Chem Biodivers ; : e202400788, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38934531

ABSTRACT

This review focus on the terpenoids as potential therapeutic agents for depression and anxiety disorders, which naturally found in a variety of plants and exhibit a wide range of biological activities. Among the terpenoids discussed in this review are α-pinene, ß-caryophyllene, α-phellandrene, limonene, ß-linalool, 1, 8-cineole, ß-pinene, caryophyllene oxide, p-cymene, and eugenol. All of these compounds have been studied extensively regarding their pharmacological properties, such as neuroprotective effect, anti-inflammation, antibacterial, regulation of neurotransmitters and antioxidant effect. Preclinical evidence are reviewed to highlight their diverse mechanisms of action and therapeutic potential to support antidepressant and anxiolytic properties. Additionally, challenges and future directions are also discussed to emphasize therapeutic utility of terpenoids for mental health disorders. Overall, this review provides a promising role of terpenoids as novel therapeutic agents for depression and anxiety, with potential implications for the development of more effective and well-tolerated treatments in the field of psychopharmacology.

8.
Chem Biodivers ; : e202401257, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39283969

ABSTRACT

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.

9.
Bull Exp Biol Med ; 177(4): 460-464, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39264562

ABSTRACT

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.


Subject(s)
Anti-Anxiety Agents , Anxiety , Brain-Derived Neurotrophic Factor , Dipeptides , Mice, Inbred BALB C , Animals , Brain-Derived Neurotrophic Factor/pharmacology , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/chemistry , Male , Female , Dipeptides/pharmacology , Dipeptides/chemistry , Rats , Mice , Anxiety/drug therapy , Maze Learning/drug effects , Behavior, Animal/drug effects
10.
Bull Exp Biol Med ; 177(5): 648-652, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39340623

ABSTRACT

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.


Subject(s)
Anti-Anxiety Agents , Vocalization, Animal , Animals , Anti-Anxiety Agents/pharmacology , Mice , Vocalization, Animal/drug effects , Male , Anxiety/drug therapy , Maze Learning/drug effects , Diterpenes/pharmacology , Benzodiazepines/pharmacology , Elevated Plus Maze Test , Behavior, Animal/drug effects , Ultrasonics , Alkaloids
11.
Dokl Biochem Biophys ; 518(1): 372-375, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39023670

ABSTRACT

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.


Subject(s)
Anxiety , Mice, Inbred ICR , TRPV Cation Channels , Animals , TRPV Cation Channels/metabolism , Anxiety/metabolism , Anxiety/drug therapy , Mice , Male , Central Nervous System/metabolism , Central Nervous System/drug effects , Anti-Anxiety Agents/pharmacology , Behavior, Animal/drug effects
12.
Curr Hypertens Rep ; 25(10): 335-341, 2023 10.
Article in English | MEDLINE | ID: mdl-37581768

ABSTRACT

PURPOSE OF REVIEW: Benzodiazepines, due to their anxiolytic properties, are prescribed to reduce anxiety and insomnia. They might have hypotensive effect via potentiation of the inhibitory effect of gamma-amino butyric acid (GABA) in the central nervous system and vasodilatory properties. However, studies comparing the effect of benzodiazepines in lowering blood pressure (BP) are equivocal. This systematic review and meta-analysis was planned to assess the efficacy of benzodiazepines in reducing blood pressure in short term among hypertensive patients. RECENT FINDINGS: Various trials and retrospective analysis conducted previously have reported that benzodiazepines cause short- as well as long-term BP reduction in patients with increased anxiety with hypertension. On the other hand, several studies investigating the efficacy of benzodiazepines in patients with hypertension have reported inconclusive results. The primary question about the effect of benzodiazepines in lowering BP remains unanswered. In this meta-analysis of seven studies, benzodiazepines were found comparable to standard drugs in reducing systolic and diastolic BP in patients having hypertension. Although, the mean difference in systolic BP with benzodiazepines and placebo was statistically not significant, the difference can be considered as clinically meaningful. The current review offers preliminary evidence that benzodiazepines may have antihypertensive properties and may be used as add-on antihypertensive in a subset of patients in short term. The existing data are encouraging, but more clinical trials and mechanistic research are required to ascertain the long-term benefits.


Subject(s)
Hypertension , Hypotension , Humans , Blood Pressure , Antihypertensive Agents/pharmacology , Hypertension/drug therapy , Benzodiazepines/therapeutic use , Benzodiazepines/pharmacology , Retrospective Studies
13.
J Pharmacol Sci ; 151(3): 135-141, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36828615

ABSTRACT

Previous pharmacological data have shown the possible existence of functional interactions between µ- (MOP), κ- (KOP), and δ-opioid receptors (DOP) in pain and mood disorders. We previously reported that MOP knockout (KO) mice exhibit a lower stress response compared with wildtype (WT) mice. Moreover, DOP agonists have been shown to exert antidepressant-like effects in numerous animal models. In the present study, the tail suspension test (TST) and forced swim test (FST) were used to examine the roles of MOP and DOP in behavioral despair. MOP-KO mice and WT mice were treated with KNT-127 (10 mg/kg), a selective DOP agonist. The results indicated a significant decrease in immobility time in the KNT-127 group compared with the saline group in all genotypes in both tests. In the saline groups, immobility time significantly decreased in MOP-KO mice compared with WT mice in both tests. In female MOP-KO mice, KNT-127 significantly decreased immobility time in the TST compared with WT mice. In male MOP-KO mice, however, no genotypic differences were found in the TST after either KNT-127 or saline treatment. Thus, at least in the FST and TST, the activation of DOP and absence of MOP had additive effects in reducing measures of behavioral despair, suggesting that effects on this behavior by DOP activation occur independently of MOP.


Subject(s)
Morphinans , Receptors, Opioid, mu , Male , Female , Mice , Animals , Morphinans/pharmacology , Antidepressive Agents/pharmacology , Analgesics, Opioid/pharmacology , Pain/drug therapy
14.
CNS Spectr ; 28(1): 53-60, 2023 02.
Article in English | MEDLINE | ID: mdl-34593077

ABSTRACT

BACKGROUND: Despite frequent benzodiazepine use in anxiety disorders, the trajectory and magnitude of benzodiazepine response and the effects of benzodiazepine potency, lipophilicity, and dose on improvement are unknown. METHODS: We performed a meta-analysis using weekly symptom severity data from randomized, parallel group, placebo-controlled trials of benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in anxiety was evaluated as a function of medication, disorder, time, potency, lipophilicity, and standardized dose and compared among benzodiazepines. RESULTS: Data from 65 trials (73 arms, 7 medications, 7110 patients) were included. In the logarithmic model of response, treatment effects emerged within 1 week of beginning treatment (standardized benzodiazepine-placebo difference = -0.235 ± 0.024, CrI: -0.283 to -0.186, P < .001) and placebo response plateaued at week 4. Doses <6 mg per day (lorazepam equivalents) produced faster and larger improvement than higher doses (P = .039 for low vs medium dose and P = .005 for high vs medium dose) and less lipophilic benzodiazepines (beta = 0.028 ± 0.013, P = .030) produced a greater response over time. Relative to the reference benzodiazepine (lorazepam), clonazepam (beta = -0.217 ± 0.95, P = .021) had a greater trajectory/magnitude of response (other specific benzodiazepines did not statistically differ from lorazepam). CONCLUSIONS: In adults with anxiety disorders, benzodiazepine-related improvement emerges early, and the trajectory and magnitude of improvement is related to dose and lipophilicity. Lower doses and less lipophilic benzodiazepines produce greater improvement.


Subject(s)
Benzodiazepines , Lorazepam , Adult , Humans , Benzodiazepines/therapeutic use , Benzodiazepines/pharmacology , Lorazepam/therapeutic use , Bayes Theorem , Anxiety Disorders/drug therapy , Anxiety/drug therapy
15.
Doc Ophthalmol ; 147(1): 15-28, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37302110

ABSTRACT

PURPOSE: To determine the association between age and retinal full-field electroretinographic (ERG) measures in companion (pet) dogs, an important translational model species for human neurologic aging. METHODS: Healthy adult dogs with no significant ophthalmic abnormalities were included. Unilateral full-field light- and dark-adapted electroretinography was performed using a handheld device, with mydriasis and topical anaesthesia. Partial least squares effect screening analysis was performed to determine the effect of age, sex, body weight and use of anxiolytic medication on log-transformed ERG peak times and amplitudes; age and anxiolytic usage had significant effects on multiple ERG outcomes. Mixed model analysis was performed on data from dogs not receiving anxiolytic medications. RESULTS: In dogs not receiving anxiolytics, median age was 118 months (interquartile range 72-140 months, n = 77, 44 purebred, 33 mixed breed dogs). Age was significantly associated with prolonged peak times of a-waves (dark-adapted 3 and 10 cds/m2 flash p < 0.0001) and b-waves (cone flicker p = 0.03, dark-adapted 0.01 cds/m2 flash p = 0.001). Age was also significantly associated with reduced amplitudes of a-waves (dark-adapted 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.005) and b-waves (light-adapted 3 cds/m2 flash p < 0.0001, dark-adapted 0.01 cds/m2 flash p = 0.0004, 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.007) and flicker (light-adapted 30 Hz 3 cds/m2 p = 0.0004). Within the Golden Retriever breed, these trends were matched in a cross-sectional analysis of 6 individuals that received no anxiolytic medication. CONCLUSIONS: Aged companion dogs have slower and reduced amplitude responses in both rod- and cone-mediated ERG. Consideration of anxiolytic medication use should be made when conducting ERG studies in dogs.


Subject(s)
Electroretinography , Pets , Adult , Humans , Animals , Dogs , Aged , Child , Cross-Sectional Studies , Dark Adaptation , Photic Stimulation
16.
Phytother Res ; 37(5): 2144-2167, 2023 May.
Article in English | MEDLINE | ID: mdl-37039741

ABSTRACT

Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of drugs to treat these disorders, which can have several adverse effects, treatment resistance, dependence, and drug-drug interactions making it necessary to search for new therapeutic agents. In particular, diazepam (DZP), a prototype drug from the group of benzodiazepines, has been commonly used and evaluated for its efficacy and safety in different anxiety disorders in clinical trials. DZP is also the most widely used reference standard in in vivo pharmacological assays of natural compounds. However, translating the results obtained in different rodent species and physiological anxiety tests instead of psychopathological animal models that can be of clinical application remains challenging. A systematic review of scientific articles published between 2010 and 2020 that included in vivo pre-clinical tests to define the anxiolytic, sedative and/or hypnotic effect of flower extracts is proposed. PRISMA and Rayyan were used for the selection of studies using four databases (Pubmed, Scopus, Web of Science, and QInsight), using the keywords: "Animals," "Anxiolytic," "Diazepam," "Elevated Plus Maze," "Flower Extracts," "Insomnia," "In vivo," "Mice," "Open Field Test," "Pre clinical" and "Sedative." The characteristics of anxiety studies in animal models, other studies related to locomotor activity, and the hypnotic effect of the extracts were compiled. Twenty-four articles were included, 21 of them performed the animal model of anxiety-like behavior of the elevated plus maze, seven the open field test, and six the light-dark box test. The locomotor activity was evaluated in 10 studies after the administration of the extracts to the animals to define their sedative effect, where only one defined that the extract (Matricaria chamomilla) had a sedative effect. The plants declared with this type of activity were Achyranthes aspera, Alcea aucheri, Brassica nigra, Cananga odorata, Carthamus tinctorius, Chrysanthemum indicum, Citrus aurantium, Couroupita guianensis, Echium amoenum, Erythrina berteroana, Gardenia jasminoides, Hibiscus tilliaceus, Lavandula officinalis, Lawsonia inermis, Matricaria chamomilla, Melia azedarach, Nerium oleander, Passiflora incarnata, Plumeria rubra, Salix aegyptiaca, Syzygium aromaticum, Tagetes erecta, Tilia americana. Although this review showed that some flower extracts have an anxiolytic effect as effective as diazepam, their therapeutic utility in anxiety disorders remains to be extensively demonstrated. Hence, more reliable and predictive behavioral tests and appropriate strategies for the experimental designs are needed to obtain more conclusive evidence with clinical significance.


Subject(s)
Anti-Anxiety Agents , Oils, Volatile , Mice , Animals , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/therapeutic use , Hypnotics and Sedatives/pharmacology , Research Design , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Anxiety/drug therapy , Diazepam/pharmacology , Oils, Volatile/pharmacology , Maze Learning , Flowers , Behavior, Animal
17.
J Emerg Med ; 64(3): 289-294, 2023 03.
Article in English | MEDLINE | ID: mdl-36925442

ABSTRACT

BACKGROUND: Droperidol is a butyrophenone, with antiemetic, sedative, anxiolytic, and analgesic properties. Although droperidol was once widely used in both emergency and perioperative settings, use of the medication declined rapidly after a 2001 U.S. Food and Drug Administration (FDA) boxed warning called the medication's safety into question. OBJECTIVE: The purpose of this clinical review was to provide evidence-based answers to questions about droperidol's safety and to examine its efficacy in its various clinical indications. DISCUSSION: Droperidol is an effective sedative, anxiolytic, analgesic, and antiemetic medication. As a sedative, when compared with haloperidol, droperidol has faster onset, as well as greater efficacy, in patients experiencing acute psychosis, with no increase in adverse events. As an antiemetic, droperidol has been found to have equal or greater efficacy in reducing nausea and vomiting than ondansetron and metoclopramide, with similar adverse effects and the added effect of reducing the need for rescue analgesia in these patients. As an analgesic, droperidol is effective for migraines and has opioid-sparing effects when used to treat abdominal pain. Droperidol is a particularly useful adjunct in patients who are opioid-tolerant, whose pain is often difficulty to manage adequately. CONCLUSIONS: Droperidol seems to be effective and safe, despite the boxed warning issued by the FDA. Droperidol is a powerful antiemetic, sedative, anxiolytic, antimigraine, and adjuvant to opioid analgesia and does not require routine screening with electrocardiography when used in low doses in otherwise healthy patients before administration in the emergency department.


Subject(s)
Droperidol , Emergency Service, Hospital , Humans , Analgesics/therapeutic use , Analgesics, Opioid/therapeutic use , Anti-Anxiety Agents/therapeutic use , Antiemetics/therapeutic use , Droperidol/therapeutic use , Hypnotics and Sedatives/therapeutic use , Ondansetron/therapeutic use , Pain/drug therapy
18.
Int J Mol Sci ; 24(7)2023 Apr 04.
Article in English | MEDLINE | ID: mdl-37047687

ABSTRACT

Major depression is one of the most common psychiatric disorders worldwide, usually associated with anxiety. The multi-etiological nature of depression has increased the search for new antidepressant molecules, including irisin, for which, in a previous study, we tested its effect in young mice when administered intraperitoneally in a long-term intermittent manner. Here, we evaluated the effect of subcutaneous short-term irisin administration (100 µg/Kg/day/5 days) in male and female mice subjected to behavioral paradigms: Tail Suspension Test (TST), Forced Swim Test (FST), Elevated Plus Maze (EPM), and Y Maze (YM). Moreover, a qRT-PCR assay was performed to analyze the impact of irisin treatment on Pgc-1α/FNDC5 expression in the brain. A significant reduction in immobility time in TST and FST was observed in irisin-treated mice. Furthermore, irisin treatment significantly increased the number of entries and time spent in open arms, demonstrating its anxiolytic effect. Memory-enhancing effects were not reported in YM. Interestingly, no gender differences were observed in all behavioral tests. Overall, these results suggest that short-term subcutaneous irisin administration can exert an antidepressant and anxiolytic role, probably due to the activation of the Pgc-1α/FNDC5 system in the brain. Further investigation could lead to the identification of irisin as a new agent for the treatment of psychiatric disorders.


Subject(s)
Anti-Anxiety Agents , Depression , Mice , Male , Female , Animals , Depression/drug therapy , Depression/metabolism , Fibronectins/metabolism , Anxiety/drug therapy , Antidepressive Agents/pharmacology , Anti-Anxiety Agents/pharmacology , Behavior, Animal
19.
Molecules ; 28(23)2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38067445

ABSTRACT

The common daisy (Bellis perennis) belongs to the family Asteraceae and, in recent years, some new research has been published on the bioactive compounds and biological activities of its extracts. In 2014, the knowledge was partially summarized, but several new studies have been published in the last nine years. In addition, the substances were tabularly consolidated to give a comprehensive overview of over 310 individual components, compound classes, and bioactivities, as well as their accurate plant organ origin. The latest results have shown that the plant has antioxidative, antimicrobial, anticancerogenic, wound healing, antidepressive, anxiolytic, nephroprotective, and insulin mimetic effects, as well as an effect on lipid metabolism. Some studies in the field of homeopathy were also listed. Ideally, a biological effect and one or several compound(s) can be correlated. However, the compounds of the extracts used have often been qualified and quantified, but it remains unclear which of these substances have an activity. The works often stick at the level of the crude extract or a fraction, but not at a single purified and tested compound and, consequently, they are hampered by a missing comprehensive bioactivity workflow. This review provides a critical overview and gaps and offers a basis for further research in this area.


Subject(s)
Anti-Infective Agents , Asteraceae , Antioxidants/metabolism , Anti-Infective Agents/metabolism , Wound Healing , Asteraceae/metabolism , Flowers , Plant Extracts/pharmacology , Plant Extracts/metabolism
20.
Molecules ; 28(7)2023 Mar 27.
Article in English | MEDLINE | ID: mdl-37049749

ABSTRACT

This review article is the second in a series aimed at providing an in-depth overview of Lavandula x intermedia (lavandin). In part I, the biology and chemistry of lavandin were addressed. In part II, the focus is on the functional properties of lavandin and its applications in industry and daily life. While reviewing the biological properties, only original research articles employing lavandin were considered. Lavandin essential oil has been found to have antioxidant and biocidal activity (antimicrobial, nematicidal, antiprotozoal, insecticidal, and allelopathic), as well as other potential therapeutic effects such as anxiolytic, neuroprotective, improving sleep quality, antithrombotic, anti-inflammatory, and analgesic. Other lavandin preparations have been investigated to a much lesser extent. The research is either limited or inconsistent across all studies, and further evidence is needed to support these properties. Unlike its parent species-Lavandula angustifolia (LA)-lavandin essential oil is not officially recognized as a medicinal raw material in European Pharmacopeia. However, whenever compared to LA in shared studies, it has shown similar effects (or even more pronounced in the case of biocidal activities). This suggests that lavandin has similar potential for use in medicine.


Subject(s)
Anti-Infective Agents , Lavandula , Oils, Volatile , Lavandula/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Plant Oils/pharmacology , Anti-Infective Agents/pharmacology , Antioxidants/pharmacology
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