Significant Central Nervous System Depressant 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.

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.

COMPARATIVE STUDY OF AQUEOUS AND ETHANOLIC EXTRACT OF AMORPHOPHALLUS PAEONIIFOLIUS TUBER ON CENTRAL NERVOUS SYSTEM ACTIVITY IN MICE

Objective: The objective of the present study was to perform phytochemical screening and to carry out a comparative study on aqueous and ethanolic extract of Amorphophallus paeoniifolius tuber on central nervous system (CNS) activity in Swiss albino mice. Methods: A. paeoniifolius tuber was collected, shed dried, and powdered. Extracts of the powder were prepared separately using ethanol and water. Phytochemical screening was also done from the extract. The animals were divided in six groups. Group 1 received DMSO solution (Control). Group 2 animals received Diazepam (1.5 mg/kg, standard). Groups 3 and 4 received A. paeoniifolius aqueous extract (200 mg/kg and 400 mg/kg, respectively). Groups 5 and 6 received A. paeoniifolius ethanolic extract (200 mg/kg and 400 mg/kg, respectively). In vivo CNS activities of the extracts were checked by actophotometer, rotarod, and forced swim test. Results: The extracts show presence of alkaloids, flavonoids, steroids, terpenoids, reducing sugar, carbohydrate, and tannin. The aqueous and ethanolic extract of A. paeoniifolius tuber showed significant decrease in locomotor activity when compared to control. Among the extracts, the 400 mg/kg ethanolic extract shows maximum CNS depression. All the extracts showed significant muscle relaxant similar to the standard drug. The extracts also exhibited significant increase in immobility time in a dose-dependent manner in forced swim test. Conclusion: The aqueous and ethanolic extract of A. paeoniifolius tuber (200 mg/kg, 400 mg/kg) shows significant CNS depressant and muscles relaxant and anxiolytic properties.

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.

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.

Neuropharmacological evaluation of methanolic extract of Costus speciosus Linn. rhizome in Swiss albino mice

Objective: To evaluate the neuropharmacological properties of Costus speciosus (C. speciosus) rhizome using different experimental mouse models. Methods: The anxiolytic effect was investigated by hole-board test, elevated plus maze and light/dark test, while central nervous system (CNS) depressant effect was evaluated by thiopental sodium-induced sleep test. Finally, antidepressant effect was evaluated by forced swimming test and tail suspension test. Results: In both elevated plus maze and hole board test, 400 mg/kg C. speciosus showed more significant CNS depressant effect than 1 mg/kg diazepam. Both 200 mg/kg and 400 mg/kg C. speciosus extract produced a significant dose-dependent decrease in onset of sleep. In forced swimming test, C. speciosus rhizome showed a decrease in duration of immobility in a dose-dependent manner. Imipramine (10 mg/kg) and C. speciosus extract at 400 mg/kg dose exhibited a significant reduction in duration of immobility in tail suspension test which provided additional evidence of antidepressant effect of C. speciosus rhizome. Conclusions: Our study indicates that C. speciosus rhizome possesses CNS depressant, anxiolytic and antidepressant-like activities. Further studies are warranted determine the exact phytoconstituents and mechanism of action responsible for the neuropharmacological effect.

Evaluation of Analgesic and Central Nervous System Depressant Effects of Holarrhena antidysenterica Stem on Swiss Albino Mice Model

Plants are astonishing reservoir of bioactive natural compounds; many of these are able to exhibit outstanding biological activities in animals. Holarrhena antidysenterica is widely used as a traditional medicine. Aim of the present study was to investigate the possible analgesic and central nervous system (CNS) depressant effects of methanol (MHAS), petroleum ether (PHAS), chloroform (CHAS), dichloromethane (DHAS) and aqueous (AHAS) extracts of the H. antidysenterica stem. The analgesic effect was evaluated by acetic acid induced writhing and hot plate methods at 50 and 100 mg/kg dose. The CNS-depressant effect was assessed by using open field, hole cross and head deep tests at 100 and 200 mg/kg dose. All the extracts had exhibited significant (Pb &lt; 0.01, Pa &lt; 0.001) analgesic and CNS depressant effects at dose dependant manner. CHAL showed maximum analgesic and CNS-depressant effect. It had shown 71.34% inhibition of abdominal writhing and 70.39% elongation of paw licking time at 100mg/kg dose. In CNS-depressant study, it exhibited 88.51% inhibition in open field (locomotion), 83.20% inhibition in hole cross (locomotion) and 85.15% inhibition (head deeping) in head deep test at 200mg/kg dose. Among the five extracts CHAL is a potent analgesic and CNSdepressant agent.Bangladesh Pharmaceutical Journal 20(2): 205-212, 2017

False-Positive Carbamazepine Results by Gas Chromatography-Mass Spectrometry and VITROS 5600 Following a Massive Oxcarbazepine Ingestion.

A 23-month-old patient with a seizure disorder presented to the emergency department after a suspected unintentional ingestion of his seizure medication. He had significant central nervous system depression and seizure-like movements. Although at the time of presentation it was known that the patient ingested his antiseizure medication, the name of the medication was not known. Also, it was not clear if the patient coingested any other drug. Broad-spectrum urine drug screening by immunoassay and GC-MS that includes presumptive screening of >200 drugs and toxins was ordered. Additionally, volatile screening for ethanol, methanol, acetone, and isopropanol was ordered. Carbamazepine testing that is available on a stat basis on the Vitros 5600 Chemistry Analyzer was also requested. Urine drug screening by GC-MS (GC-7890, MS-5975; Agilent) showed the presence of carbamazepine and oxcarbazepine. Carbamazepine concentration measured by immunoassay on the Vitros 5600 Chemistry Analyzer (Ortho-Clinical Diagnostics) was 7.9 μg/mL (therapeutic range, 4–12 μg/mL). Unless there was a coingestion of another drug, the patient's symptoms of central nervous system depression and seizure-like movements were not consistent with the reported carbamazepine level. Because the presence of carbamazepine was reported on both GC-MS and immunoassay methods, it was thought that the patient ingested carbamazepine. Owing to the presence of oxcarbazepine on the GC-MS, it was thought that the …

Retrospective Chart Review of Synthetic Cannabinoid Intoxication with Toxicologic Analysis.

IntroductionUse of synthetic cannabinoids (SC) has recently emerged as a new drug epidemic. Our emergency departments (EDs) received a surge of SC users presenting with lethargy and bradycardia, contrasting prior reports of SC-induced tachycardia and agitation. Our goal was to describe these novel presentations and characterize the compounds.MethodsWe present a case series of patients with SC intoxication who presented to our toxicology service covering two tertiary care EDs between 2/11/2015 and 6/23/2015. A retrospective chart review recorded initial vital signs, chief complaint and clinical course. Urine, blood and xenobiotic samples were analyzed using either liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry. We compared resulting spectra against databases containing numerous SCs or metabolites and scored based on a reference comparison.ResultsBetween 2/11/2015 and 6/23/2015, we identified 141 visits. Males comprised 139 visits (age range 21–68 years; median 35, interquartile range 20). Sixty-eight percent presented with lethargy or loss of consciousness. Hypotension (SBP <90 mmHg) and bradycardia (HR<60 bpm) were seen in 10% and 24% of visits, respectively. While most patients were discharged after observation, three were admitted to the intensive care unit and seven to telemetry. Admissions were for vital sign instability, bradycardia requiring pacing, prolonged sedation and respiratory failure requiring mechanical ventilation.Laboratory analysis revealed SC in the XLR-11 family in 18/36 drug, 9/12 blood, and 23/31 urine samples. Carboxamide indazole derivative (CID) family compounds were detected in 13/36 drug samples, 21/31 urine samples, but no blood samples; 11/31 drug samples contained both XLR-11 and CID. Other compounds detected included PB-22 and nicotine. No JWH compounds, opiates, imidazoline receptor agonists, benzodiazepines or other sedative-hypnotics were detected.ConclusionUnlike their predecessors, novel SC may be associated with significant central nervous system depression and bradycardia. While prior reports indicated that SC mostly contained JWH compounds, none were detected in these samples. The most commonly identified compounds in this series were CID and alkyl SC derivatives, such as INACA compounds and XLR-11. These tend to be full agonists at the cannabinoid receptor and are presumably more potent. The lack of other depressants suggests that the clinical findings are due to the combination of these compounds and not coingestants or adulterants. SC intoxication should be considered for patients with undifferentiated psychomotor depression and bradycardia.

In vivo CNS Depressant and Antinociceptive Studies of Microcos paniculata Stem Extracts on Animal Model

The main objective of the study was to evaluate the possible central nervous system (CNS) depressant and antinociceptive effects of methanol (MMPS), petroleum ether (PMPS), chloroform (CMPS), dichloromethane (DMPS) and aqueous (AMPS) extracts of the Microcos paniculata (M. paniculata). The CNS-depressant effect of different extracts of M. paniculata stem on Swiss albino mice was assessed by using open field, hole cross and head deep tests at 100 and 200 mg/kg dose. Analgesic effect was evaluated by acetic acid-induced writhing and hot plate methods at 100 and 200 mg/kg dose. All the extracts had exhibited significant (Pb &lt; 0.01, Pa &lt; 0.001) CNS depressant and analgesic effects in a dose dependant manner. MMPS had shown highest CNSdepressant effect with 93.39% inhibition of mice movement (open field), 78.92% inhibition of hole cross and 86.90% inhibition of head deeping at 200 mg/kg dose. Besides, DMPS extracts showed maximum analgesic effect with 75.52% inhibition of abdominal writhing and 65.55% elongation of paw licking time at 200mg/kg dose. Among the five extracts, MMPS possesses potent CNS depressant effect while DMPS possesses potent analgesic effect. These findings may expose effectiveness of the extracts on anxiety and pain that may help to formulate a herbal medicine or to search a lead compound.Bangladesh Pharmaceutical Journal 20(1): 39-45, 2017

Hypnotic effect of the essential oil from the leaves of Myrtus communis on mice.

BackgroundMyrtus communis has been suggested as a sleep aid in unconventional medicine. Moreover, previous studies have also indicated its sedative- and hypnotic-like activity. In this study, the hypnotic effect of M. communis was investigated.MethodsEssential oil (EO) of M. communis (600, 800, and 1,000 mg/kg) was given orally to Swiss albino mice of both sex, and the hypnotic effect was evaluated. In addition, the EO of M. communis (500, 600, 800, and 1,000 mg/kg) was administered orally to Swiss albino mice of both sex 60 minutes prior to pentobarbital injection (50 mg/kg). Latency to sleep and sleep duration were recorded. The effect of the EO on motor coordination and muscle relaxation was evaluated using chimney and traction tests, 60 and 90 minutes after administration of the respective doses of the EO, respectively.ResultsThere was no induction of hypnosis as the presence of the righting reflex was intact. However the EO prolonged pentobarbital-induced sleeping time and there was also 50% negative response on the chimney and traction test in a dose dependent manner.ConclusionThe EO of M. communis did not produce a hypnotic effect, but it potentiated a hypnotic effect with significant central nervous system depressant activity.

First Pharmacological Therapy for Hypoactive Sexual Desire Disorder in Premenopausal Women: Flibanserin.

To review data regarding flibanserin, a recently approved therapy for hypoactive sexual desire disorder (HSDD). Literature search of MEDLINE (September 1995 to November 2015) was performed using the search term flibanserin. Reference lists from included articles were reviewed for pertinent citations. We included phase-3 trials of flibanserin as a treatment for HSDD. Four reports of phase-3 trials were included. One extension study of four phase-3 trials and one phase-2 pharmacokinetic trial were also included. Though a strong placebo response was demonstrated, flibanserin consistently, yet marginally, showed improvement (compared with placebo) in the number of satisfying sexual events per month. The most common adverse events were dizziness (11.4%), somnolence (11.2%), nausea (10.4%), fatigue (9.2%), insomnia (4.9%), and dry mouth (2.4%). Flibanserin is effective in the treatment of HSDD. Flibanserin should be administered at bedtime to limit the risk for hypotension/syncope, accidental injury, and central nervous system (CNS) depression. Concomitant alcohol use contributes to significant CNS depression and hypotension/syncope with flibanserin and should be avoided according to the boxed warning. Careful patient assessment prior to the diagnosis of HSDD and the use of flibanserin is needed for safe use. Prescribing guidelines recommend discontinuing flibanserin at 8 weeks in the absence of benefit. Sexual dysfunction should be addressed in a patient-specific manner. Providers should exercise shared decision making in prescribing flibanserin for HSDD and discuss flibanserin's benefits and alternative options.

Neuroprotective effects of Nigella sativa extracts during germination on central nervous system.

Background: Nigella sativa Linn. which has many acclaimed medicinal properties is an indigenous herbaceous plant and belongs to the Ranunculaceae family, which grows in countries bordering the Mediterranean Sea, Pakistan and India.Objective:This study was designed to investigate the effects of N. sativa seed extracts of different germination phases on the central nervous system (CNS) responses in experimental animals.Materials and Methods:Anxiolytic, locomotor activity of extracts (1 g/kg of body weight) was evaluated in both stressed and unstressed animal models and antiepileptic effect was evaluated by maximal electroshock seizure model keeping diazepam (20 mg/kg) as a positive control. Antidepressant effect was evaluated by forced swim test and tail suspension test keeping imipramine (15 mg/kg) as a positive control.Results:All tested extracts of N. sativa during different phases of germination (especially 5th day germination phase) showed significant (P < 0.001) anxiolytic effect in comparison to control. Diazepam reduced locomotor activity in control (unstressed) rats but did not show affect in stressed rats while N. sativa extracts from germination phases significantly (P < 0.001) reduced locomotor activity in unstressed as well as stressed animals. All the extracts of N. sativa from different germination phases exhibited significant (P < 0.001) reduction in various phases of epileptic seizure on comparison with the reference standard (diazepam). During antidepressant test, N. sativa extracts exhibited a slight reduction in the immobility of rats.Conclusion:During germination, especially in 5th day germination extract, N. sativa showed significant CNS depressant activity as compared to whole seeds that possibly may be due higher content of secondary metabolites produced during germination.

Evaluation of Analgesic, Anti-inflammatory and CNS Depressant Potential of Dendrophthoe falcata (Linn.) Leaves Extracts in Experimental Mice Model

Plants are extraordinary reservoir of bioactive natural products, many of which exhibit chemical and structural features on outstanding biological activities in animals. Dendrophthoe falcata (Linn.) is an important parasitic plant extensively used in folk medicine. In this regard, the aim of this study was to investigate the possible analgesic, anti-inflammatory and central nervous system (CNS) depressant activities of ethanol, aqueous, chloroform and petroleum ether extracts of D. falcata (Linn.) leaves (AEDFL, EEDFL, CEDFL and PEDFL) on Swiss albino mice. The analgesic activity was determined by tail immersion and acetic acid induced writhing methods at a dose of 50, 100 and 200 mg/kg, p.o. using morphine sulfate as a standard drug at a dose of 5mg/kg of body weight. Carrageenan-induced paw edema model was applied to find out anti-inflammatory potential at the same doses of analgesic activity. Here ibuprofen was treated as a standard drug at 10mg/kg body weight. The CNS depressant effect of the extracts were evaluated by using open field and hole cross tests. All the extracts exhibited significant (P b < 0.01, P a < 0.001) analgesic, antiinflammatory and CNS depressant effects at dose dependant manner. Petroleum ether extracts (PEDFL) showed maximum analgesic effect (77.45% inhibition of abdominal writhing and 82.12% elongation of tail withdrawal time) at 200mg/kg dose. Moreover, the highest anti-inflammatory potential (90.24% inhibition of paw edema volume) was showed by petroleum ether extract at 200mg/kg dose. On the other hand, ethanol extract (EEDFL) proved to have significant (97.33% and 85.91% inhibition of locomotion in open field and

Central Nervous System Depressant, Analgesic and Antidiarrheal Effects of the Seed Extracts of &lt;i&gt;Dimocarpus longan&lt;/i&gt; Lour in Rats

Purpose: To assess the central nervous system (CNS) depressant, analgesic and antidiarrheal activities of the dried seed crude extracts of Dimocarpus longan Lour in rodents.Methods: Selected pharmacological effects of the ethanol (ENLS), petroleum ether (PELS), chloroform (CHLS) and ethyl acetate (EALS) extracts of D. longan fruit seeds were investigated. CNS depressant activity was evaluated by open field and hole cross tests; analgesic activity by acetic acid-induced writhing test and formalin-induced licking test; and anti-diarrheal activity was assessed in castor oil and magnesium-induced diarrhea rat model. The extracts were given orally in a rat model at doses of 200 and 300 mg/kg body weight. Normal saline served as control in all experiment. In CNS depressant test, diazepam (1 mg/kg) was used as reference drug while indomethacin (10 mg/kg) and loperamide(2 mg/kg) were used as standard drugs in analgesic and antidiarrheal tests, respectively.Results: In hole cross method, EALS showed the most effective depressant effect, viz, 1.17±0.17 for 200 mg/kg dose and 0.83±0.31 number of movements for 300 mg/kg dose after 120 min (p &lt; 0.01), whereas in the open field test, all the extracts exhibited significant (p &lt; 0.01) depressant effect in relation to positive control, diazepam. In acetic acid-induced pain test, PELS gave the lowest number of writhing (2.83±0.307) and the highest inhibition (88.45 %, 300 mg/kg dose) which was statistically significant. All the extracts also significantly (p &lt; 0.01) suppressed licking activity in both phases of the formalin-induced licking test, in contrast to indomethacin. In the antidiarrheal tests, diarrheal suppression was highest at 300 mg/kg dose for all the extracts, compared with loperamide in both castor oil and magnesium sulphate induced diarrhea model.Conclusion: The extracts of Dimocarpus longan tested demonstrated significant CNS depressant, analgesic and antidiarrheal activities in a rodent model.Keywords: Dimocarpus longan Lour, CNS depressant, Analgesic, Anti-diarrheal.

Investigation of in vivo neuropharmacological effect of Alpinia nigra leaf extract

To analyze in vivo neuro-pharmacological effects of Alpinia nigra as anxiety is a particular form of behavioral inhibition that occurs in response to novel environmental events. In present study, the extract of Alpinia nigra was evaluated for its central nervous system depressant effect using mice behavioral models, such as hole cross, open field and thiopental sodium induced sleeping time tests for its sedative properties and an elevated plus-maze test for its anxiolytic potential, respectively. In anxiolytic study, the extract displayed increased percentage of entry into open arm at the dose of 400 and 200 mg/kg. The extract produced a significant (P<0.01) increase in sleeping duration and reduction of onset of sleep compared to sodium thiopental at both doses (200 and 400 mg/kg). The extract (200 and 400 mg/kg) also showed a dose-dependent suppression of motor activity and exploratory activity of the mice in both open field and hole cross test. This study demonstrates that the treated extract has significant central nervous system depressant effect. Further studies on active constituent of the extract can provide approaches for therapeutic intervention.

Pediatric Zolpidem Ingestion Demonstrating Zero-Order Kinetics Treated With Flumazenil

Zolpidem is a widely prescribed anti-insomnia agent. Although most pediatric zolpidem ingestions are benign, large ingestions can cause significant central nervous system (CNS) depression. Flumazenil has been reported to reverse the CNS effects of zolpidem. We describe a case of a large pediatric zolpidem ingestion resulting in profound CNS depression that responded to flumazenil administration. Serial zolpidem serum levels confirmed the ingestion. A 10-year-old boy with trisomy 21 presented to the emergency department 1 hour after he was found sedate with several zolpidem 5-mg tablets in his mouth. Seventeen tables (85 mg) were unaccounted for from a prescription bottle. He became unarousable approximately 2 hours after his ingestion. Flumazenil 0.2 mg intravenously was given with rapid return to his baseline mental status. He became resedate 1 hour later but was arousable. Sixteen hours after his presentation, he was asymptomatic. Serial zolpidem serum levels were obtained, showed an initial level of 310 ng/mL, and demonstrated zero-order kinetics. Zolpidem is an imidazopyridine, which binds to the benzodiazepine receptor. It is rapidly absorbed and has a short-half life. Unintentional pediatric ingestions of zolpidem are typically well tolerated. However, this case demonstrates that large ingestions may cause significant and prolonged CNS depression. Flumazenil, a benzodiazepine receptor antagonist, has been described to reverse the effects of zolpidem in adult ingestions. There are few published reports describing flumazenil use in pediatric ingestion patients. This case suggests that flumazenil may be an effective treatment for zolpidem-induced CNS depression in the pediatric patient.

Antinociceptive activity of methanol extract of flowers of Impatiens balsamina

Ethnopharmacological relevanceImpatiens balsamina Linn. (Balsaminaceae), an annual herb locally called “Dopati”, is cultivated as an ornamental garden plant in Bangladesh. Flowers of the plant are used in folk medicine to treat lumbago, neuralgia, burns and scalds. Aim of the studyThis study evaluated the antinociceptive effect of the methanol extract of I. balsamina flowers (MIB). Materials and methodsThe extract was evaluated for antinociceptive activity using chemical- and heat-induced pain models such as acetic acid-induced writhing, hot plate, tail immersion and formalin test. To verify the possible involvement of opioid receptor in the central antinociceptive effect of MIB, naloxone was used to antagonize the effect. The effect of MIB on central nervous system (CNS) was also studied using hole cross and open field tests. ResultsMIB demonstrated strong and dose-dependent antinociceptive activity in all the chemical- and heat-induced mice models (p<0.05). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. The use of naloxone confirmed the association of opioid receptors in the central antinociceptive effect. MIB also showed significant central nervous system depressant effect (p<0.05). ConclusionThis study reported the peripheral and central antinociceptive activity of the flowers of I. balsamina and rationalized the traditional use of the flower in the treatment of different painful conditions.

Neuropharmacological Activity of Trigonella foenum graecum Linn. Seeds

Objective: To evaluate the neuropharmacological activity of Trigonella foenum graecum (Fenugreek) seeds. Methods: Total alcoholic extract (TA), Total aqueous extract (TQ), Petroleum ether extract (PE), Total alkaloidal extract (TK), Total glycosidal extract (TG), Fenugreek oil (FO), Diosgenin (DI) and Trigonelline (TR) were assessed for their neuropharmacological activity in primary screening studies, locomotor activity and phenobarbitone induced sleeping time using albino Wistar rats. The extracts TA, TQ, PE and FO were administered 100 mg/kg b.w. and TK, TG, DI and TR were administered 50 mg/kg b.w. intraperitoneally. Caffeine (CF) (48 mg/kg) and Chlorpromazine hydrochloride (CP) (150 μg/kg) were used as standard drugs. Results: In all the studies, all the extracts and active principles except TQ showed significant central nervous system (CNS) stimulant activity, while TQ alone showed significant CNS depressant activity. Conclusion: Thus from the above studies, the active compounds present in the fenugreek seed extracts possess CNS stimulant and depressant activities.

Are one or two dangerous? Opioid exposure in toddlers

Ingestions of opioid analgesics by children may lead to significant toxicity as a result of depression of the respiratory and central nervous systems. A review of the medical literature was performed to determine whether low doses of opioids are dangerous in the pediatric population under 6 years old. Methadone was found to be the most toxic of the opioids; doses as low as a single tablet can lead to death. All children who have ingested any amount of methadone need to be observed in an Emergency Department (ED) for at least 6 h and considered for hospital admission. Most other opioids are better tolerated in ingestions as small as one or two tablets. Based on the limited data available for these opioids, we conclude that equianalgesic doses of 5 mg/kg of codeine or greater require 4 to 6 h of observation in the ED. Data for propoxyphene and all extended-release preparations are limited; their prolonged half-lives would suggest the need for longer observation periods. All opioid ingestions leading to respiratory depression or significant central nervous system depression require admission to an intensive care unit.