Central Nervous System Depressant Activity Research Articles

Acute toxicity (LD50 values) and neuropharmacological profile of n-hexane fraction of Petiveria alliacea L. (Phytolaccaceae) in mice

Background: Petiveria alliacea L. (Phytolaccaceae) ethnomedically is known for its sedative property and beneficial treatment of other central nervous system (CNS) disorders. However, the neuropharmacological properties of the n-hexane extract of this aromatic plant leaf have not been reported, hence this study. Objective: To determine the acute toxicity profile (LD50) and some CNS activities of the n-hexane extract of fresh leaf of P. alliacea (NHEPA) in mice. Method: The fresh leaf of Petiveria alliacea was collected and the n-hexane extract obtained using appropriate technique. The LD50 was determined for both the oral and intraperitoneal (i.p.) route. All treatments were administered via i.p. route. Behavioural activity was evaluated using the novelty-induced behaviour (NIB) to assess rearing, grooming and locomotion; sedative activity was tested on ketamine-induced hypnosis while the anticonvulsant potential was assessed using chemo-convulsants. The mechanism of action was determined using amphetamine as agonist and flumazenil as an antagonist. Results: The LD50 values obtained for the extract was 2450 and 346 mg/kg for oral and intraperitoneal routes respectively. The extract displayed significant CNS depressant activity on all NIB parameters. NHEPA significantly prolonged sleep latency and total sleeping time at 100 and 150 mg/kg. i.p. The extract also offered some mild protection against convulsion across the model used. The probable mechanism of action may include inhibition of monoamine pathways and augmentation of the GABAA- benzodiazepine complex pathway. Conclusion: NHEPA showed CNS depressant activity, exhibited significant sedative activity and mild anticonvulsant activity.

Neuropharmacological study of Moringa olifera

Objective: Moringa olifera is a medicinal plant widely used in many parts of the world for hypertension, pain and epilepsy. The aim of this study was to determine the effect of M. olifera aqueous leaf, root and steam extract on neurobehavioral activities of healthy mice. Method: Male mice were randomly divided into a control group (given 0.9% NaCl orally) and three groups treated with the extract at doses of 100, 200, and 400 mg/kg/day for 14 consecutive days. Neuropharmacological activity were evaluated by neuro-muscular coordination (rota rod treadmill), pain (hot plate and acetic acid-induced abdominal constriction). Administration of M. olifera extract had a significant and dose dependent antinociceptive action in both thermal and chemical tests (p < 0.05). The extract (400 mg/kg) caused a reduction in exploration activity and neuromuscular coordination, and decreased the mobility time in the FST, suggesting an antidepressant-like action. Motor activity was not significantly affected by any of the doses used. Conclusion: The results suggest that the plant aqueous extract may have a dose-dependent central nervous system (CNS) depressant action.

Study of Central Nervous System Depressant and Behavioral Activity of Ethanolic Extract of Clitoria Annuain Albino Rats

Objective: The objective was to evaluate depressant effects on central nervous system (CNS) and behavioral effects of ethanol extract of clitoria annua and to find the phytochemical responsible for these activities with possible mode of action. Materials & Method: The central nervous system (CNS) depressant activity of C. annua was evaluated by the classical models of depression as Rota rod method, Actophotometer test, tail suspension, and thiopental sodium induced sleeping time tests in Rat. The Rats were divided into Normal, Standard, and two test groups containing five rats each. The test groups received extract at the doses of 200, and 400 mg/kg body weight orally where as the Normal group received distilled water (0.1 ml/mice, p.o.). Diazepam (2 mg/kg, i.p.) was used as standard drug. Results: It is clear that the plant extract significantly decreased the locomotor activity of rats in Rota rod method and Actophotometer test when compared to the normal (p < 0.05). It is observed that the extract showed significantly (p < 0.05) increased in immobility time in tail suspension test in mice. In addition, the extract produced prolongs the sleeping time with onset of action in contrast to the normal group. Conclusions: The present work depicts the evaluation of possible CNS depressant activity of C. annua in mice models. EECA can be a safe and effective approach/alternative for the treatment of number of CNS depressant disorders. More extensive study is required to fractionate, purify, and identify the exact mechanism of action CNS Depressant activity present in ethanolic extract of Clitoria annua with its active ingredients.

Caution in usage of clobazam in elderly patients

Clobazam, one of the newer benzodiazepines, is now used extensively as first add on therapy in focal epilepsy.A 67-year-old diabetic and hypertensive gentleman with a history of frontal contusion one year ago, presented with clustering of seizures. He was started on clobazam 20 mg, and levetiracetam 1000 mg/day. Recurrence of seizures prompted a dose escalation of clobazam to 40 mg/day. The patient developed hepatic encephalopathy and his decompensation was probably precipitated by the use of high dose of clobazam. Clobazam was thus gradually tapered off along with hepatic precoma regimen, and other supportive measures leading to an uneventful recovery.Caution must be taken while administering clobazam to elderly and debilitated patients or those with organic brain syndrome as they are more prone to the central nervous system (CNS) depressant activity of benzodiazepines. Since clobazam requires dealkylation and hydroxylation prior to conjugation, it should be used with caution in patients with hepatic involvement.

Phytochemical investigation and exploration of the central nervous system depressant activity of ethanolic extract of the flowers of Jasminum grandiflorum L. as folklore medicine in Swiss albino mice

Background: In Indian traditional medicine, the flowers of Jasminum grandiflorum L. (Oleaceae) are claimed to possess powerful central nervous system (CNS) depressant activity. Despite these traditional claims, no in-depth scientific study has been performed on the CNS depressant activity of the flowers of J. grandiflorum. Therefore, the present study was aimed at evaluating the CNS depressant activity of an ethanolic extract of the flowers of J. grandiflorum in Swiss albino mice.
 Methods: Acute oral toxicity tests were done at doses of 550, 1750, and 5000 mg/kg. The extract was also subjected to phytochemical tests and TLC tests. The CNS depressant activity of the EEJG was evaluated by various models, such as the forced swimming test, tail suspension test, thiopental sodium-induced sleeping time test, locomotor activity test, and muscle co-ordination test, at two different doses (500 and 1000 mg/kg) in Swiss albino mice. Diazepam (1 mg/kg) was used as a standard drug.
 Results: In acute oral toxicity studies, the extract was found to be safe up to a dose level of 5000 mg/kg body weight. EEJG at both doses (500 and 1000 mg/kg) showed significantly (p<0.05, p<0.01) increase in immobility time in the forced swimming test and tail suspension test. In the thiopental-induced sleeping time test, EEJG at 1000 mg/kg showed a significant (p<0.05) effect on the onset of action time and also significantly (p<0.01) increase the duration of sleeping time. EEJG at 1000 mg/kg showed a significant (p<0.01) decrease in locomotor activity, and the EEJG at both doses (500 and 1000 mg/kg) showed a significantly (p<0.05, p<0.01) decreased in muscle co-ordination activity when compared to control group.
 Conclusions: The present study confirms the significant CNS depressant activity of the ethanolic extract of the flowers of J. grandiflorum, which may be due to flavonoids and steroids present in the extract as phytoconstituents confirmed by TLC. This study supports the plant's traditional use as a CNS depressant.

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.

Chemical Constituents, Medicinal, and Pharmacological Applications, and Toxicology of Fructus Zizyphi

Fructus Zizyphi refers to the fruits of Zizyphus jujuba plant, and this plant is geographically distributed in East Asia and South Europe. This plant belongs to the family Rhamnaceae, and this plant is a shrub of 10 m in height. This review aimed to focus on chemical constituents, medicinal and pharmacological applications, and the toxicology of Fructus Zizyphi. The major chemical constituents of Fructus Zizyphi are triterpenes and triterpene saponins. Fructus Zizyphi treats insomnia, increases body weight, strengthens body muscle, decreases body temperature, increases urine volume, accelerates women's period, calms and reinforces agents, chases phlegm, treats vision, skin inflammation, hepatitis, respiratory diseases, diabetes, gastric ulcer, and different skin wounds. The pharmacology of Fructus Zizyphi includes experimental pharmacology and clinical pharmacology. Experimental pharmacology includes antiallergenic, anti-inflammatory, analgesic, anti-hyperglycemic, anti-hypercholesterolemic, central nervous system depressant, immune stimulation, and platelet aggregation activities. Fructus Zizyphi ethanol extracts to mice in drinking water daily for 3 months without any effect on animal death, hematology, organ weight, or sperm secretion. Fructus Zizyphi was not mutagenic. Fructus Zizyphi declined gastric adenocarcinoma progress. Fructus Zizyphi without general precautions, drug connections; drug and laboratory test relations; teratogenic or non-teratogenic effects in pregnancy; nursing mothers; or pediatric use. In conclusion, Fructus Zizyphi had antiallergenic, anti-inflammatory, analgesic, anti-hyperglycemic, anti-hypercholesterolemic, central nervous system depressant, immune stimulation, platelet aggregation activities, and without any effect on animals death, hematology, organ weight or sperm secretion.

Anxiolytic-like activity of Aloysia virgata var. platyphylla leaves extract in mice

Background: Medicinal plants are part of traditional medicine and should be considered a therapeutic alternative for mental diseases. Several plants belonging to the Verbenaceae family have proved useful in treating general anxiety disorders, the most prevalent psychiatric disorders. Objective: This research aimed to verify the extract’s safety, the effect on general behavior, and the effect on sleeping time, as well as to evaluate the anxiolytic-like effect of the methanol extract of Aloysia virgata var. platyphylla (Avp), in mice. Methodology: The toxicity test was done according to the OECD guide (mice groups n=5), and general behavior was observed during the assay. Sleeping time was assessed using the pentobarbital-induced hypnosis method (n=8). Male Swiss albino mice (n=6) were treated with 50 to 400 mg/kg of Avp extract and diazepam as a control. The anxiolytic-like effect was tested through the hole board and elevated plus-maze test. Results: The Avp extract has no side effects in tested doses, and no central nervous system depressant activity was noted. A. virgata var. platyphylla increased exploration (number and time) in the hole board. In the elevated plus-maze, increased number and time into open arms were evidenced compared to the control group. Conclusion: With all these results, we concluded that the Avp extract is safe and has a potential anxiolytic-like activity in the animal model used.

A REVIEW ON WITHANIA SOMNIFERA (L.) DUNAL- AS AN IMPORTANT AYURVEDA PLANT

Withania somnifera (L.) Dunal is a well-known and important medicinal plant widely used in several indigenous systems of medicine for the treatment of various ailments, viz. asthma, bronchitis, inflammatory diseases, ulcer and stomach problems. Steroidal lactones have been reported as the major phytoconstituents of this species. Different pharmacological experiments in a number of in vitro and in vivo models have convincingly demonstrated the ability of W. somnifera to exhibit anti-inflammatory, anti-oxidative, antimicrobial, anti-anxiety, aphrodisiac, immunomodulation, anti- diabetic, anti-ulcer, anticancer, central nervous system depressant and hepatoprotective activities, lending support to the rationale behind several of its traditional uses. The species is also used to treat some neurological disorders like Parkinson’s and Alzheimer’s. The phytochemicals such as withaferin A, withanolide A and withanolide D isolated from this plant are potential bioactive molecules. Due to the remarkable biological activity of W. somnifera and its constituents, it will be appropriate to develop them as a medicine and make them more potent by chemical modifications and biotransformation. This review has covered botany, chemistry and pharmacology of the plant besides its traditional and folkloric uses.

Central Nervous System Activity of 1-aryl-2(thiomethylene benzimidazol-2-yl)-4-(phenyl/p-chlorophenyl)-imidazoles and 1-aryl-2-sulphono-[benzimidazol-2-yl]-methyl-4-(phenyl/p-chlorophenyl)-imidazoles

1-Aryl-2-mercapto-4-(phenyl/p-chlorophenyl)-imidazoles (Ia-1) were condensed with 2-chloromethyl benzimidazole (II) in presence of sodium hydroxide in ethanol to get 1-aryl-2-thiomethylene benzimidazol-2-yl-4-(phenyl/p-chlorophenyl)-imidazoles (IIIa-1). These compounds (IIIa-1) were subsequently oxidised by hydrogen peroxide to get 1-aryl-2-sulphono-[benzimidazol-2-yl]-methyl-4 and (phenyl/p-chlorophenyl)-imidazoles (Iva-1). All the compounds (IIIa-1) and (Iva-1) exhibited central nervous system depressant action on albino mice. All the compounds are non-toxic and possess some sedative activity.

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of Erythrina Alkaloids

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of <i>Erythrina</i> Alkaloids

Central nervous system depressant activity of fractions of Globimetula braunii Engl. (Loranthaceae) growing on Terminalia catappa L. (Combretaceae) and isolation of lupeol

Globimetula braunii is a parasitic plant belonging to the family Loranthaceae. Traditionally, the plant has been reported to be used in the treatment of insomnia. The study was carried out to investigate the central nervous system (CNS) depressant activity of the fractions of Globimetula braunii growing on Terminalia catappa and to isolate the phytochemical compound(s) present in the most active fraction. The CNS depressant activity of all the fractions was investigated using diazepam induced sleep. The most active fraction was further subjected to the hole board test and beam walk assay. The chromatographic technique was used for the isolation of phytochemical compound. Hexane fraction significantly (p&lt;0.05) reduced latency to sleep and prolonged the sleeping time. Both chloroform and ethylacetate fractions at highest and median doses showed significant increase in the duration of sleep compared to normal saline. The n-butanol fraction at all doses tested do not have any effect on time of onset and duration of sleep when compared with normal saline treated group. Hexane fraction significantly (p&lt;0.05) decreased the number of head dip in a dose dependent manner and delayed the time to reach the goal box compared to normal saline treated group. Lupeol was isolated from n-hexane fraction.

Central nervous system depressant activity of ethanol extract of Motandra guineensis (Thonn) AD. aerial parts in mice

BackgroundMotandra guineensis Thonn AD. (Apocynaceae) is used for the management of pain and as a sedative in the treatment of insanity in Nigerian traditional medicine. The study investigated the neuropharmacological activities of the aerial parts of M. guineensis in mice. MethodsClassical models of tail suspension, forced swim, open field, hole board, elevated plus maze, and sodium pentobarbital-induced sleeping time tests were employed and the extract was administered at doses of 50,100 and 200 mg/kg, p.o. Oral acute toxicity test was done at the dose of 2000 mg/kg. The extract was also subjected to phytochemical tests and GC–MS analysis. ResultsIn tail suspension test, the extract at the dose of 200 mg/kg significantly reduced immobility time of mice compared to control while in the forced swim test, immobility time of the mice decreased in a dose-dependant manner. In the open field test, there was a significant and dose-dependant reduction in the number of lines and squares crossed compared with control. The number of head dips in the hole-board test was decreased in the extract treated groups compared to control. The extract significantly increased the time spent in the open arms of elevated plus-maze apparatus at higher doses (100 and 200 mg/kg) compared to control. The phenobarbitone-induced sleeping time was prolonged by the extract at all doses compared to control. There was no death recorded for the extract at the dose of 2000 mg/kg. ConclusionThe results indicate possible CNS depressant effect of the ethanol extract of M. guineensis, thus support the use of the plant as a sedative in the treatment of insanity in Nigerian traditional medicine.

An Overview on Chemical Constituents, Medicinal Applications, Pharmacological Activity, Toxicology, Metabolism and Pharmacokinetics of Strobilus lupuli

Strobilus lupuli is the dried strobiles (inflorescences) of Humulus lupulus L. (Cannabaceae). Other names of Strobilus lupuli include European hops, hoblon, hop vine, hopfen, and hops. Humulus lupulus L. is an important plant that contains metabolites used in the brewing and pharmaceutical fields. Strobilus lupuli is cultivated in Europe, Asia, and North America, occurring in the world's temperate areas. The analysis of Strobilus lupuli through chromatography analysis showed the presence of bitter substances and xanthohumol. The bitter substances in the resins are the major constituents of Strobilus lupuli, where these substances represent 15-25% of Strobilus lupuli constituents. Strobilus lupuli is applied as a sedative agent for the treatment of nervous tension and insomnia. Strobilus lupuli is applied in the treatment of dyspepsia and lack of appetite. Strobilus lupuli is applied to treat anemia, bacterial infections, abdominal cramps, dysmenorrhoea, leukorrhoea, dermatitis, diarrhea, migraine, and edema. The pharmacology activity of Strobilus lupuli includes experimental and clinical pharmacology. Experimental pharmacology includes antimicrobial, anti-inflammatory, antioxidant, central nervous system depressant, estrogenic and miscellaneous activities. The oral median lethal dose of ethanol extract of Strobilus lupuli in mice was found to be 500 mg/kg, while the oral median lethal dose of Strobilus lupuli in rats was 2700 mg/kg. No information is available on general precautions or on precautions concerning drug and laboratory test interactions. There is no teratogenic effect in pregnancy, or nursing mothers, or pediatric use of Strobilus lupuli. Strobilus lupuli powder dose = one dose of 0.5 g. Infusion or decoction dose = 0.5 g/ 150 ml water. Strobilus lupuli extract dose = 0.06-0.08g.

Deciphering the CNS anti-depressant, antioxidant and cytotoxic profiling of methanol and aqueous extracts of Trametes versicolor and molecular interactions of its phenolic compounds.

The present study sought to evaluate the central nervous system (CNS) depressant, antioxidant, and cytotoxicity activity of methanol and aqueous extract of Trametes versicolor (METV and AETV). The CNS activity was assessed by the open field, hole-cross, forced swimming, thiopental sodium-induced sleeping time, hole-board, and rotarod tests in Swiss albino mice. For both extracts, a substantial decrease in locomotion was observed in open field and hole-cross tests. In addition, the molecular docking study has been implemented through Maestro V11.1. The higher dose of METV (400 mg/kg) and the lower dose of AETV (200 mg/kg) exhibited a significant decrease in immobility time in forced swimming test and increased prolongation of sleep in thiopental sodium-induced sleeping time test, respectively. In contrast, a moderate finding was observed for the hole-board and rotarod tests. Additionally, a significant DPPH scavenging assay and a high toxicity effect in brine shrimp lethality assay were observed. Besides, five phenolic compounds, namely baicalin, quercetin, catechin, p-hydroxybenzoic acid, and quinic acid, were used for the molecular docking study, whereas catechin demonstrated the highest binding affinity towards the targets. The findings conclude that the T. versicolor could be an alternative source for CNS anti-depressant and antioxidant activity.

Behavioural activities and chemical composition of fresh leaf essential oil of Plectranthus aegyptiacus from Southwest Nigeria in mice

Objectives: This study determined the chemical composition of essential oil obtained from fresh leaf of Plectranthus aegyptiacus, and evaluated it for novelty-induced behavioural (NIB) and determine its mechanism(s) of action in mice. Methods: The oil was hydro-distillated, and analyzed using gas chromatography-mass spectrometry. The effects of the oil (50, 100 and 150 mg/kg; i.p., n=6) on novelty-induced behavioural was assessed using open field test and head dipping on hole board. Probable mechanism(s) were evaluated using antagonists: flumazenil, naloxone and cyproheptadine at 2 mg/kg each, atropine and yohimbine at 5 mg/kg and 1 mg/kg respectively. Key Findings: The LD50 values obtained were 2154 and 490 mg/kg for oral and intraperitoneal routes respectively. The oil (50, 100 and150 mg/kg) significantly (p&lt;0.05, 0.01 and 0.01) inhibited all NIB and head dips. Flumazenil significantly (p&lt;0.05) reversed the effect of the oil on NIB; atropine, naloxone and cyproheptadine significantly (p&lt;0.01, 0.01 and 0.001) potentiated inhibitory effect on NIB respectively, while yohimbine showed no significantly effect. The analyzed oil showed 61 compounds, and the major compounds were carvacrol, germacrene-D, p-cymene and [1,1'-Bicyclopentyl]-2,2'-diol. Conclusions: The study concluded that the oil possessed central nervous system depressant activity, which could be mediated mainly through augmentation of GABAergic neurotransmission, while cholinergic-(muscarinic), adrenergic and serotonergic pathways may be involved.

New therapeutic agents marketed in 2020: Part 1

New therapeutic agents marketed in 2020: Part 1

Evaluation of Central Nervous System depressant action of catharanthus roseus G. Don leaves in mice

Evaluation of Central Nervous System depressant action of catharanthus roseus G. Don leaves in mice

The spontaneous motor action of alcoholic excerpt of Withania coagulans fruits in Swiss albino mice by Actophotometer

People spend about one third of their life in sleeping. The various sedative and hypnotic drugs currently used have various adverse drug reactions. In 1977 Budhiraja et al. have done insufficient work on the Withania coagulans – a susceptible species that is not found plentiful in the world. Therefore, it was critical to discover the Central Nervous System (CNS) depressant activities of alcoholic extract of Withania coagulans fruits in Swiss albino mice by means of actophotometer. The spontaneous locomotor action was assessed by means of the actophotometer. The CNS depressant medications reduce the exploratory action in rodent as they weaken the motor coordination so that rodent is stationary for a considerable time. Thus, there is fewer interruptions to the rays of light. This spontaneous locomotor movement duration is statistically compared with the control, standard and the test drugs. There was statistically highly significant (p-value &amp;#60; 0.001) relationship witnessed between alcoholic excerpt of Withania coagulans fruits with spontaneous locomotor action in Swiss albino mice on the photoactometer. The alcoholic excerpt of Withania coagulans fruits established the CNS depressant action in Swiss albino mice by photoactometer.

Assessment of Neuropharmacological Profile of Ethanolic Extract of Lawsonia Inermis Flowers

On preliminary basis neuropharmacological profile of ethanolic extract of flowers of Lawsonia inermis was carried out. For assessing the activity of flowers on central nervous system locomotor activity using actophotometer, muscle relaxant activity using rotarod apparatus, pentobarbital-induced hypnosis and anticonvulsant activity by maximal electroshock test was performed. Ethanolic extract of flowers of Lawsonia inermis decreased the motor activity by 48.63 % and showed 49.03% noteworthy muscle relaxation along with 127.73% potentiation of pentobarbital-induced sleeping time and 66.67% decreased the duration of tonic hind leg extension of seizures activity. The results conclude that the extract of flowers of Lawsonia inermis has significant central nervous system depressant activity. Further investigations are, however, necessary to explore mechanism(s) of action involved in these pharmacological activities.