Central Nervous System Depressant Effects Research Articles

Vasorelaxant effects of ellagitannins isolated from Cuphea carthagenensis.

Cuphea carthagenensis (Jacq.) J. F. Macbr. is a popular plant in Brazilian folk medicine owing to its hypotensive and central nervous system depressant effects. This study aimed to validate the hypotensive effect of the plant's aqueous extract (AE) in rats and examine the vascular actions of three hydrolyzable tannins, oenothein B, woodfordin C, and eucalbanin B, isolated from AE. Systolic blood pressure in unanesthetized rats was determined using the non-invasive tail-cuff method. Oral treatment of normotensive rats with 0.5 and 1.0 g/kg/day AE induced a dose-related hypotensive effect after 1 week. In rat aortic rings pre-contracted with noradrenaline, all ellagitannins (20 - 180 µM) induced a concentration-related vasorelaxation. This effect was blocked by either removing the endothelium or pre-incubating with NG-nitro-l-arginine methyl ester (10 µM), an inhibitor of nitric oxide (NO) synthase. In KCl-depolarized rat portal vein preparations, the investigated compounds did not affect significantly the maximal contractile responses and pD2 values of the concentration-response curves to CaCl2. Our results demonstrated the hypotensive effect of C. carthagenensis AE in unanesthetized rats. All isolated ellagitannins induced vasorelaxation in vitro via activating NO synthesis/NO release from endothelial cells, without altering the Ca2+ influx in vascular smooth muscle preparations. Considering the low oral bioavailability of ellagitannins, the determined in vitro actions of these compounds are unlikely to account for the hypotensive effect of AE in vivo. It remains to be determined the role of the bioactive ellagitannin-derived metabolites in the hypotensive effect observed after oral treatment of unanesthetized rats with the plant extract.

Central nervous system depressant effect of ethanol extract of Senna spectabilis (DC.) H.S.Irwin & Barneby in mice

Context: Senna spectabilis (DC.) H.S.Irwin & Barneby which belongs to Fabaceae family is widely used traditionally in the treatment of various diseases and disorders such as constipation, insomnia, anxiety, epilepsy, malaria and skin diseases. Aims: To investigate the central nervous system (CNS) depressant effect of 70% ethanol extract of S. spectabilis leaves (70SSEE) using different neuropharmacological models in mice. Methods: The CNS depressant effect of 70SSEE was investigated by the classical models of depression as elevated plus maze (EPM), hole cross (HC), and thiopental sodium (TS)-induced sleeping time tests in mice. The EPM test was used to assess the anxiolytic activity of 70SSEE at doses of 10, 50, and 100 mg/kg, while HC and TS-induced sleeping time tests at doses of 100, 250, and 500 mg/kg were used to assess the locomotor and sedative activity in mice. Results: In EPM test, 70SSEE at doses of 50 and 100 mg/kg significantly (p<0.05) increased the number of open arm entries and time spent in open arm by mice compared to controls. In HC test, 70SSEE significantly inhibited the movement of animals across the hole in a dose-dependent manner. In addition, the administration of 70SSEE to mice significantly (p<0.05) decreased sleep latency time and increased sleep duration of TS-induced mice. Conclusions: 70SSEE has CNS depressant effects which is a rational explanation for its use in traditional medicine. From these findings, it is hoped that this plant could be used in the treatment of various neurological disorders, including anxiety and insomnia.

Evaluation of the Neurobehavioural Toxicity Potential of Aqueous Ethanol Extracts of Leaf/Seed of Datura metel, Mucuna pruriens, and Tapinanthus globiferus Growing on Azadirachta indica Host Tree in Mice

Aqueous ethanol extracts of Mucuna pruriens seed (AEMPS), Datura metel leaf (AEDML) and seed (AEDMS), and Tapinanthus globiferus (AETGL) Growing on Azadirachta indica host tree are being evaluated for their anxiolytic, antidepressant, anti-parkinsonian, and addictive activities in other studies. The aim of this study was to investigate the liability or otherwise of extracts of the selected medicinal plants for some benzodiazepines-related neurobehavioural toxicities in mice. Actophotometry was used for the evaluation of the locomotory activity related to central nervous system depressant (cns) effect, diazepam-induced sleep potentiation for hypnotic liability, rodent beam (rod)-walking assay for balance and motor co-ordination, and novel object recognition test (NORT) for cognitive deficit evaluation. The results indicate, compared to negative control (distilled water) treatment mean values of 4.69±0.95 % locomotory activity reduction, 430.71±16.80 sec. sleep onset and 168.43±10.56 min. duration, 5.00±0.00 balance/motor co-ordination performance, and 54.41±1.99 novel object recognition, treatments with high oral doses of AETGL and AEMPS (1500 mg/kg each) did not significantly negatively impact these behavioural indices but even enhanced novel object recognition. High oral doses of AEDML and AEDMS (750 mg/kg each), and tramadol (133 mg/kg) caused significant (p<0.05) 42.24±2.64, 27.73±2.17, and 36.74±4.44, mean % locomotory activity reductions, 196.86±10.12, 193.88±15.39, and 189.14±18.31 second mean sleep onsets and 319.71±18.85, 309.57±20.27, and 356.00±26.01 minute mean sleep durations, 1.67±0.42, 1.30±0.40, 1.833±0.48 mean balance/motor co-ordination performances, and 40.49±5.45, 31.33±5.23, 19.37±3.96 mean novel object recognitions, respectively. Diazepam (2 mg/kg) treatment caused 33.71±2.19 mean % locomotory activity reduction, 1.33±0.49 mean balance/motor co-ordination performance, and 29.91±2.81 mean novel object recognitions. Additionally, most mouse groups exposed to tramadol, AEDML, and AEDMS extracts displayed unusual (hallucination-like, predator-like) fearful trepidations when in proximity with the novel objects. These findings indicate AETGL and AEMPS extracts may be devoid of neurobehavioural toxicities but tramadol, diazepam, AEDML and AEDMS extracts may be liable to significant sedative, hypnotic, myo-relaxant, and anti-cognitive effects. These findings justify the traditional uses of Tapinanthus species and Mucuna pruriens extracts for the treatment of memory deficits and related neurological disorders. They also justify the morbid and fatal toxicity risks associated with the use of Datura metel extracts, tramadol, and the benzodiazepines.

Fentanyl concentrations in ligated femoral blood in the presence and absence of NPS benzodiazepine drugs. A review of over 1250 benzo-dope / fentanyl toxicity cases in Alberta, Canada

The drug combination referred to as ‘benzo dope’ has become prevalent in recent years, with an increasing number of fentanyl-related deaths reporting the concomitant presence of one or more benzodiazepine drug, such as etizolam, flualprazolam and flubromazepam. The central nervous system (CNS) depressant effects of these benzodiazepine drugs can exacerbate respiratory and CNS depressant effects resulting from the use/misuse of potent opioids such as fentanyl. This combined and enhanced drug-induced toxicity can pose a significant threat to life. Over a three-year period (2020–2022), the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada issued 2812 case reports with fentanyl detected; of these cases, approximately 45% (1261) were positive for at least one benzodiazepine drug. This study presents concentrations of both fentanyl and benzodiazepine drugs in post mortem blood collected from a visualized, ligated femoral vein. The study demonstrates that the blood concentration of fentanyl in benzo-dope case reports is considerably higher than in cases where no benzodiazepine drug was detected.The median concentration of fentanyl in femoral blood for cases that also contained a benzodiazepine drug was 12.4 ng/mL (2020), 11.9 ng/mL (2021) and 14.0 ng/mL (2022). The median concentration of fentanyl in femoral blood for cases that did not contain a benzodiazepine drug was 8.5 ng/mL (2020), 7.0 ng/mL (2021) and 7.2 ng/mL (2022). The percent differences between the groups were similar with those observed from quantitative analysis of drug powders from unrelated police seizures in Alberta, Canada, suggesting the observed differences in blood fentanyl concentration may be due to the use of a drug substance with a higher concentration of fentanyl.Furthermore, the reported concentration of the benzodiazepine drug(s) is low, such that the role/contribution, if any, that this drug may have played in the decedents’ death should be questioned and carefully considered by the certifying medical examiner/coroner.

Comparison of Dexmedetomidine and Dexamethasone as an Adjuvant to Bupivacaine in Onset and Interval of Supraclavicular Nerve Block

Aim: To compare duration and onset of motor and sensory block by using dexmedetomidine and dexamethasone as adjuvant to bupivicaine in supraclavicular brachial plexusblock. Place and duration of study: Department of Anaesthesiology, Surgical Intensive Care & Pain Management, Civil Hospital, Dow University of Health Sciences Karachi from 29th June 2022 to 29th December 2022. Design: Randomized controlled trial study Methodology: Sixty patientswere enrolled in the study that had an elective upper-limb surgery performed under supraclavicular anesthesia of hand, wrist, forearmand elbow were allocated through randomization into two groups. Thirty patients in group A treated with bupivacaine 25 ml of 0.5% with dexamethasone 8mg (2 ML) and 30 in group B treated with bupivicaine 25 ml of 0.5% with dexmedetomidine 1µg/kg (2ml). Patients were observed in post-anesthesiacareunitpost-surgery. Duration of onset of pain was noted by patient’s first request for analgesia. Results:Themean age of patients was 34.88±9.39 years. Mean onset time of sensory and motor block was significantly low in group A than group B. Mean duration of sensory block and motor block was significantly high in group B than group A [813.87±113.72 vs. 752.63±27.96; p=0.006] and [734.13± 84.44 vs533.07±88.38;p=0.0005]. The time to request for 1st rescue analgesic was significantly increased in group B as compare to group A(p=0.0005). Practical Implication: Regional anesthesia in orthopedic procedures is superior to general anesthesia in terms of better postoperative pain relief, less central nervous system depressant effect of drugs and early discharge from hospital. Conclusion:The duration of block prolonged in cases where dexmedetomidine was added to the bupivacaine was longer but onset was reduced in comparison to the dexamethasone cases. Keywords: Brachial plexus block, Supraclavicular block, Dexmedetomidine, Dexamethasone

EVALUATION OF CNS DEPRESSANT AND BEHAVIORAL ACTIVITY OF AN ETHANOL EXTRACT OF ZIZIPHUS JUJUBA (BER) IN MOUSE MODEL

Objective: Ziziphus jujuba, known as Ber (Hindi), is an indigenous herb found in India. Z. jujuba has been used to treat various diseases such as respiratory system diseases (asthma, cough, and laryngitis), gastrointestinal problems (constipation, colitis, and liver diseases), as well as cardiovascular and genitourinary system diseases. Seeds and fruit have been also reported to have central nervous system (CNS) depressant effect. Hence, in this study, neuropharmacological effects of leaves are studied which are not reported previously. Z. jujuba extract’s potential to depress the CNS and affect behavior was examined in this study, along with the phytochemicals that may be responsible for these effects. Methods: 400 mg/kg of the extract was administered intraperitoneally. As a benchmark, diazepam (2 mg/kg body weight i.p.) was used. ANOVA and Dunnett’s tests were used to evaluate the data. The results were all presented as Mean (SEM) values. p>0.05 was regarded as meaningful. Result: The outcome of the study demonstrated that ethanol extract of Z. jujuba (400 mg/kg i.p.) reduced locomotion, caused muscle relaxation, and had anti-anxiety effects. Conclusions: Ethanols extract of Z. jujuba leaves exhibits CNS depressant action and significant anxiolytic activity comparable to diazepam.

Assessment of membrane stability, central nervous system depressant, and gut motility effects of Lablab purpureus seeds

Introduction: Lablab purpureus, under the family of Fabaceae, is a plant with various pharmacological activities. The present study was aimed to investigate the phytoconstituents, membrane stabilizing activity, central nervous system (CNS) depressant potential, and gastrointestinal (GI) motility of the methanol extract of L. purpureus seeds (MELPS).Methods: The methanol plant extract was screened for different phytochemical groups. Mice were classified into four groups for in vivo activities. Group-I was designated as negative control and received distilled water (10 mL/kg body weight); group-II served as positive control and received diazepam (1 mg/kg body weight). Group-III and group-IV both were experimental groups and received plant extract at 200 and 400 mg/kg body weight, respectively.Results: Alkaloids, carbohydrates, saponins, glycosides, tannins, phenols, flavonoids, and proteins were found after phytochemical analysis. On hypotonic solution-induced hemolysis of erythrocyte membrane, MELPS9 (9 mg/mL) resulted in the highest percentage of inhibition (60.51 ± 0.889), and on heat-induced hemolysis, MELPS9 (9 mg/mL) resulted in the highest percentage of inhibition (33.97 ± 0.21). In the case of the CNS depressant potential experiment, mice that received a sample at a dose of 400 mg/kg body weight showed the highest result (54.40 ± 4.51) compared with the positive control (14.2 ± 3.70) (P < 0.001). Similarly, 400 mg/kg dose sample exhibited the highest percentage of inhibition (60.51 ± 0.889) of hemolysis and GI motility (22.26%).Conclusion: It can be concluded that the MELPS has potential membrane stability, CNS depressant, and antimotility effects.

Acute exposure to abuse-like concentrations of toluene induces inflammation in mouse lungs and brain.

Toluene is an aromatic hydrocarbon commonly abused by young adolescents for its central nervous system depressant effects. Although toluene's pharmacological effects at high concentrations are relatively well-known, few studies have assessed toluene's effects on lung and brain tissues. The present study characterized the pathological effects of acute inhaled toluene exposure in the lungs and brains of male Swiss-Webster mice (N = 68). Using a static vapor exposure chamber, mice (PND 28) received a single 30-min toluene administration (0, 1000, 2000, or 4000 ppm). Lung and brain tissues were extracted 24-h post-exposure. Histology results revealed significant changes in the morphology of lung tissue (e.g., irregular cellular architecture) with the 2000- and 4000-ppm exposures expressing greater signs of pathology than control 0-ppm exposure. Markers of immune system activity (F4/80 and Ly-6G) and cellular proliferation (Ki-67) in the lung revealed no significant differences. Additionally, brain tissues were analyzed for changes of astrogliosis (glial fibrillary acidic protein [GFAP]) and oxidative stress (glutathione peroxidase [GPx]). GFAP showed increased astrogliosis in the striatum with 2000-ppm toluene showing significantly higher expression than control (p < 0.05) and a marginal effect in the hippocampus. No other markers showed significant changes. The increased signs of inflammation and cellular damage suggest that exposure to a single high concentration of toluene, typical of abuse, is capable of producing pathology in both lung and brain tissue.

Tabernaemontana arborea and ibogaine induce paroxysmal EEG activity in freely moving mice: Involvement of serotonin 5-HT1A receptors

Several Apocynaceae species, most notably Tabernanthe iboga, Voacanga africana and many Tabernaemontana species, produce ibogan-type alkaloids. Although a large amount of information exists about the Tabernaemontana genus, knowledge concerning chemistry and biological activity remains lacking for several species, especially related to their effects on the central nervous system (CNS). The aim of this study was to evaluate the effect of Tabernaemontana arborea Rose ex J.D.Sm. (T. arborea) hydroalcoholic extract (30, 56.2 and 100 mg/kg, i.p.) and two of its main alkaloids (ibogaine and voacangine, 30 mg/kg, i.p.) on electroencephalographic (EEG) activity alone and in the presence of the chemical convulsant agent pentylenetetrazole (PTZ, 85 mg/kg, i.p.) in mice. EEG spectral power analysis showed that T. arborea extract (56.2 and 100 mg/kg) and ibogaine (30 mg/kg, i.p.) promoted a significant increase in the relative power of the delta band and a significant reduction in alpha band values, denoting a CNS depressant effect. Voacangine (30 mg/kg, i.p.) provoked an EEG flattening pattern. The PTZ-induced seizures were not modified in the presence of T. arborea, ibogaine, or voacangine. However, sudden death was observed in mice treated with T. arborea extract at 100 mg/kg, i.p., combined with PTZ. Because T. arborea extract (100 mg/kg, i.p.) and ibogaine (30 mg/kg, i.p.), but not voacangine (30 mg/kg, i.p.), induced paroxysmal activity in the EEG, both were explored in the presence of a serotonin 5-HT1A receptor antagonist (WAY100635, 1 mg/kg, i.p.). The antagonist abolished the paroxysmal activity provoked by T. arborea (100 mg/kg, i.p.) but not that observed with ibogaine, corroborating the participation of serotonin neurotransmission in the T. arborea effects. In conclusion, high doses of the T. arborea extract induced abnormal EEG activity due in part to the presence of ibogaine and involving serotonin 5-HT1A receptor participation. Nevertheless, other possible constituents and mechanisms might participate in this complex excitatory activity that would be interesting to explore in future studies.

Exploring the link between adolescent inhalant misuse and suicidal behaviour: a behavioural toxicology perspective

Adolescent inhalant misuse has a known association with suicidal thoughts and behaviour. This association persists even after inhalant misuse has ceased. Previous studies have hypothesised that this association may derive from socioeconomic disadvantage or vulnerability, and potentially mediated by impulsivity. This association may also be due to the central nervous system depressant effects of inhalants. This review takes a behavioural toxicology perspective, focussed particularly on the serotonergic system and the Hypothalamic-Pituitary-Adrenal (HPA) axis, as potential links between adolescent inhalant misuse and suicidal behaviour. The challenges of bridging the pre-clinical and clinical literature in this area are discussed, along with promising avenues for future research; ultimately aimed at reducing suicide risk in a vulnerable adolescent population group.

Neuropharmacological Assessment of the Hydroethanolic Leaf Extract of Calotropis procera (Ait). R. Br. (Apocynaceae) in Mice.

Background Calotropis procera has been widely used traditionally for its analgesic and anti-inflammatory effects. It is also reportedly used in ethnomedicine for mental health disorders including epilepsy even in the absence of supporting scientific data. Thus, the potential of the plant to affect neurological functions was evaluated. Methods Irwin's test was performed to determine the effect of the oral administration of the extract (30–3000 mg kg−1) on gross behaviour and physiological function. The activity meter, rotarod, pentylenetetrazol- (PTZ-) induced convulsion, pentobarbitone-induced sleep test, and the tail immersion tests were used to evaluate the spontaneous activity, neuromuscular function, convulsive threshold, sedation, and analgesic effects of the Calotropis procera extract (30–1000 mg/kg), respectively, in mice. Results Calotropis procera extract (CPE) exhibited significant (p < 0.0001) anticonvulsant and analgesic effects. There was a significant increase in withdrawal latency of the CPE-treated animals in the tail immersion test for analgesia (p < 0.0001), while latency and duration of PTZ-induced convulsions were positively modulated. Calotropis procera extract showed significant (p < 0.0001) central nervous system depressant effects in pentobarbitone-induced hypnosis at 100–1000 mg/kg and spontaneous activity test (30–1000 mg/kg). The extract also depicted impaired motor coordination at 100–1000 mg/kg dose levels. LD50 was estimated to be above 1000 mg kg−1. Conclusions Calotropis procera extract has significant central nervous system depressant and analgesic effects in mice.

1,1-Difluoroethane Forensic Aspects for the Toxicologist and Pathologist.

1,1-Difluoroethane (DFE) is a halogenated hydrocarbon that is commonly used as a propellant in air duster products. Herein, the pharmacology of DFE was reviewed, and questions relevant to medicolegal investigations were addressed. Particular emphasis was given to detection time in biological specimens and the range, onset and duration of effects. DFE may be abused as an inhalant and is rapidly absorbed through the lungs. Onset of central nervous system (CNS) depressant effects is within seconds and the duration may only last minutes. The effects may lead to impairment of human performance, including confusion, lethargy, impaired judgment, loss of motor coordination and loss of consciousness. Death may result even after the first use. With heavy use or in combination with other CNS depressants, extended periods of drowsiness or loss of consciousness may be observed with an increased risk of a fatal event. A majority of impaired driving investigations where DFE was identified included a collision demonstrating the significant impact its use may have on traffic safety. When DFE is identified alone, without other drugs that cause CNS impairment, the effects may not be observable minutes after the crash, making identification of its use difficult. Although concentrations dissipate rapidly, DFE has been detected in blood specimens collected up to 3 hours after the driving incident. Two studies on passive exposure presented herein demonstrated that it is unlikely to detect DFE above concentrations of ∼2.6 µg/mL in blood or urine due to even extreme unintentional exposure. Alternative specimens such as brain, lung and tracheal air should be considered in some postmortem investigations. DFE has been identified in blood specimens from postmortem cases at concentrations from 0.14 to 460 µg/mL and in impaired driving cases from 0.16 to 140 µg/mL.

Polypharmacy and severe potential drug-drug interactions among older adults with cardiovascular disease in the United States

BackgroundPolypharmacy continues to be a topic of concern among older adults and puts patients at increased risk of potential drug-drug interactions (DDIs) and negative health outcomes. The objective of this study was to assess the prevalence of polypharmacy among older adults with cardiovascular disease (CVD) and to identify severe potential DDIs.MethodsA retrospective chart review was conducted in a tertiary care center over a three-month period where we reviewed home medications of older adults upon hospital admission. Inclusion criteria were age ≥ 65 years, history of CVD, and admission to the cardiology service. Polypharmacy was defined as 5 or more medications taken concomitantly, hyper-polypharmacy was defined as 10 or more medications taken concomitantly, and severe potential DDIs were considered to be those belonging to category D or X using Lexicomp® Drug Information Handbook. Category D interaction states that modification of therapy should be considered while category X states that the combination should be absolutely avoided.ResultsA total of 404 patients with a mean age of 76.6 ± 7.4 years were included. Patients were taking an average of 11.6 ± 4.5 medications at home and 385 (95%) received polypharmacy, 278 (69%) received hyper-polypharmacy, and 313 (77.5%) had at least one severe potential DDI. Under category D, the most common potential DDIs were drugs with additive central nervous system (CNS) depressant effect and drugs that increase the risk of QT prolongation. Under category X, the most common potential DDIs were non-selective β-blockers that may diminish the bronchodilator effect of β2 agonists and drugs with anticholinergic properties that enhance the ulcerogenic effect of oral solid potassium.ConclusionsPolypharmacy, hyper-polypharmacy, and severe potential DDIs are very common in older adults with CVD. Clinicians should vigilantly review patients’ drug records and adjust therapy accordingly to prevent adverse drug reactions and negative health outcomes.

Alprazolam-associated death: suicide or unintentional overdose?

ABSTRACT Alprazolam is a psychoactive triazolo-benzodiazepine, commonly prescribed for the treatment of anxiety disorders and considered safe due to its high therapeutic index. It is frequently detected in polydrug-related deaths but there are very few cases of fatal intoxication by alprazolam not in combination with alcohol or other drugs. A fatal poisoning by alprazolam in a 60-years old male physician has been reported. At autopsy, no evidence of traumatic injuries or diseases was observed except for signs of bronchopneumonia and slight hypertrophy of the left ventricle. Alprazolam and its major metabolite (α-hydroxyalprazolam) were detected in biological samples through liquid chromatography-tandem mass spectrometry (LC-MS/MS). High concentrations of alprazolam and α-hydroxyalprazolam were found, respectively, in femoral blood 0.45 and 0.03 mg/L, urine 2.12 and 0.42 mg/L, bile 1.33 and 0.56 mg/L, liver 3.81 and 0.28 mg/L. Alprazolam alone was also detected in vitreous humour (0.19 mg/L) and in stomach content (0.34 mg/L). No conclusive information confirmed the hypothesis of a suicidal ingestion of alprazolam. However, an alprazolam drug-related death was assessed based on the pre-existing cardiovascular and respiratory defects. The high levels of alprazolam several times greater than the therapeutic range contributed to death due to its respiratory and central nervous system-depressant effects.

Sintocalmy, a Passiflora incarnata Based Herbal, Attenuates Morphine Withdrawal in Mice.

Chronic opioid use changes brain chemistry in areas related to reward processes, memory, decision-making, and addiction. Both neurons and astrocytes are affected, ultimately leading to dependence. Passiflora incarnata L. (Passifloraceae) is the basis of frequently used herbals to manage anxiety and insomnia, with proven central nervous system depressant effects. Anti-addiction properties of P. incarnata have been reported. The aim of this study was to investigate the effect of a commercial extract of Passiflora incarnata (Sintocalmy®, Aché Laboratory) in the naloxone-induced jumping mice model of morphine withdrawal. In addition, glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) levels were assessed in the frontal cortex and hippocampus, and DNA damage was verified on blood cells. In order to improve solubilization a Sintocalmy methanol extract (SME) was used. SME is mainly composed by flavonoids isovitexin and vitexin. The effects of SME 50, 100 and 200mg/kg (i.p.) were evaluated in the naloxone-induced withdrawal syndrome in mice. SME 50 and SME 100mg/kg decreased naloxone-induced jumping in morphine-dependent mice without reducing locomotor activity. No alterations were found in GFAP levels, however SME 50mg/kg prevented the S100B increase in the frontal cortex and DNA damage. This study shows anti-addiction effects for a commercial standardized extract of P. incarnata and suggests the relevance of proper clinical assessment.

Importance of Herba Passiflorae in Medicinal Applications: Review on Experimental and Clinical Pharmacology

The dried aerial parts of Passiflora incarnate L. plant are called Herba Passiflorae. This plant belongs to the Passifloraceae family. This review aims to focus on the importance of Herba Passiflorae in medicinal applications with special reference to its experimental and clinical pharmacology. Herba Passiflorae possesses flavonoids and alkaloids ingredients. The major constituents of Herba Passiflorae are flavonoids such as vicenin-2, orientin, isoorientin, vitexin, and isovitexin. Herba Passiflorae is applied for the cure of dysmenorrhoea, neuralgia, and nervous tachycardia. It is a slight sedative for nervous restlessness, insomnia, and anxiety. The fruit of Herba Passiflorae is used for jams, jellies, and desserts. The juice is a favorite flavoring in drinks. The pharmacology effect of Herba Passiflorae includes experimental and clinical pharmacology. Experimental pharmacology includes analgesic, antipyretic, anti-inflammatory, antimicrobial, cardiovascular, central nervous system depressant, and uterine stimulant effects. Clinical pharmacology includes anxiolytic, analgesic, and sedative effects, as well as its effect on nausea, menopause, dysmenorrhea, and diabetes. Herba Passiflorae stimulates uterine contractions, so it is used during pregnancy. The water extract of Herba Passiflorae is not genotoxic. The passion fruit is more appropriate for children's use due to the incorporation of Lactobacillus casei in passion fruit. The daily oral intake of passion fruit at public doses is non-toxic and safe. The daily dose in adults as a sedative is 0.5-2 g of aerial parts 3-4 times. In conclusion, Herba Passiflorae has analgesic, antipyretic, anti-inflammatory, antimicrobial, cardiovascular, central nervous system depressant, uterine stimulant, anxiolytic, analgesic, and sedative effects, as well as, its effect on nausea, menopause, dysmenorrhea, and diabetes.

Alcohol and Neural Dynamics: A Meta-analysis of Acute Alcohol Effects on Event-Related Brain Potentials

BackgroundAn understanding of alcohol’s acute neural effects could augment our knowledge of mechanisms underlying alcohol-related cognitive/motor impairment and inform interventions for addiction. Focusing on studies employing event-related brain potential methods, which offer a direct measurement of neural activity in functionally well-characterized brain networks, we present the first meta-analysis to explore acute effects of alcohol on the human brain. MethodsDatabases were searched for randomized laboratory alcohol-administration trials assessing brain activity using event-related potentials. Hedges’ g coefficients were pooled using 3-level random-effects meta-regression. ResultsSixty independent randomized controlled trials met inclusion (total N = 2149). Alcohol’s effects varied significantly across neural systems, with alcohol leading to reductions in event-related potential components linked with attention (P3b), g = −0.40, 95% CI (−0.50, −0.29), automatic auditory processing (mismatch negativity), g = −0.44, 95% CI (−0.66, −0.22), and performance monitoring (error-related negativity), g = −0.56, 95% CI (−0.79, −0.33). These effects were moderated by alcohol dose, emerging as significant at doses as low as 0.026% blood alcohol concentration and increasing to moderate/large at 0.12%. In contrast, irrespective of dose, relatively small or nonsignificant alcohol effects emerged in other processing domains, including those linked to executive control (N2b responses) and stimulus classification (N2c responses). ConclusionsContrary to traditional conceptualizations of alcohol as a “dirty drug” with broad central nervous system depressant effects, results instead support accounts positing targeted alcohol effects in specific processing domains. By identifying alcohol effects on brain systems involved in performance monitoring and attention, results move toward the identification of mechanisms underlying alcohol-related impairment as well as factors reinforcing addiction.

“Central Nervous System Depressant effects and Muscle relaxant activity of Galphimia gracilis Bartl. Stem methanol extract on Swiss albino mice”

“Central Nervous System Depressant effects and Muscle relaxant activity of Galphimia gracilis Bartl. Stem methanol extract on Swiss albino mice”

Lavandulae aetheroleum Oil: A Review on Phytochemical Screening, Medicinal Applications, and Pharmacological Effects

Lavandulae aetheroleum, the oil, was obtained by vapor condensation from the flower of Lavandula angustifolia Mill. or Lavandula intermedia Loisel (Lamiaceae) plant. Other names of Lavandulae aetheroleum oil are Al birri, common or English lavender. The Lavandula angustifolia Mill. or Lavandula intermedia Loisel plant is spreading in the Mediterranean, southern Europe, Bulgaria, Russia, and USA. The Lavandula angustifolia Mill. or Lavandula intermedia Loisel plant, is an odor shrub with 1-2 m in height. The oil is a clear, colorless, or pale yellow. The gas chromatography studies reported the following percentage of the major chemical constituents in the oil: linalyl acetate (25-46%), linalool (20-45%), terpinen-4-ol (1.2-6.0%), lavendulyl acetate (&gt; 1.0%), 1,8-cineole (1,8-cineol, cineol, cineole, eucalyptol) (&lt; 2.5%), 3-octanone (&lt; 2.5%), camphor (&lt; 1.2%), limonene (&lt; 1.0%), and α-terpineol (&lt; 2.0%). Medicinal applications of the oil include the treatment of restlessness, anxiety, cardiovascular disorders, insomnia, and gastrointestinal disorders, burns, diarrhea, headache, sore throats, and wounds. Pharmacological effects include experimental and clinical pharmacology. Experimental pharmacology includes anesthetic, anticonvulsant, sedative, anti-inflammatory, antimicrobial, antispasmodic, antispasmodic, central nervous system depressant effects. Clinical pharmacology includes anxiolytic, analgesic, and cardiovascular effects. The oil dose by inhalation = 0.06-0.2 ml/ 3 times/day while oil dose internally = 1-4 drops approximately 20-80 mg on a sugar cube per day. In conclusion, Lavandulae aetheroleum oil had an anesthetic, anticonvulsant, sedative, anti-inflammatory, antimicrobial, antispasmodic, antispasmodic, central nervous system depressant, anxiolytic, analgesic, and cardiovascular effects.

Flubromazolam: Detection in five post-mortem cases.

Flubromazolam is a potent triazole benzodiazepine with moderately long-lasting central nervous system-depressant effects relative to other benzodiazepines such as commonly prescribed diazepam. Flubromazolam has been studied in the living. However, there are no published reports including measured drug concentrations in post-mortem cases. We report five cases in which flubromazolam was detected in a systematic screen using high-resolution mass spectrometry and then quantified in femoral blood. In none of the five cases was the cause of death directly attributed to flubromazolam toxicity, as there was a variety of both sedative and stimulant drugs also present. However, it is important that the drug concentrations that were measured are made available for future post-mortem forensic interpretation.