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Drug poisoning has a high incidence and serious consequences in medical institutions; its epidemiological characteristics also directly affect the changes in national laws and policies and the implementation of local management policies. Chinese statistics on drug-related abnormal death cases generally come from judicial appraisal centers and medical units. However, due to differences in work content and professional restrictions, there are differences in information management forms, which makes it difficult for appraisers to conduct a professional and systematic analysis of drug-related cases. This article focuses on the analysis of epidemiological characteristics of sedative-hypnotics and opioid painkillers and their exposure patterns in cases of poisoning death by analyzing the annual report of the American Association of Poison Control Center, combined with the characteristics of drug exposure in China.
Subject(s)
Analgesics, Opioid/adverse effects , China/epidemiology , Databases, Factual , Hypnotics and Sedatives , Poison Control Centers , United StatesABSTRACT
The aim of this study was to synthesize 1-(5-(hydroxymethyl)-4-methyl-3-oxo-3,4-dihydro-pyrazin-2-yl) guanidine (mucunaguanide),a pyrazinone alkaloid compound extracted from the seed of Stizotobium cochinchinensis.Starting from benzyloxy acetaldehyde,following four steps in reaction including condensation,cyclization,substitution and hydrogenation reaction,mucunaguanide was synthesized with total yield of 27.9％,and purity of more than 97.5％.Structures of all the intermediates and target compound were confirmed by IR,1H NMR and MS.This synthetic process was characterized with raw materials available,simple in operation with much milder reaction conditions,and was an ideal method of synthesis of this compound.
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Objective: To study the pharmacodynamics of Tianma Lingzhi Granules (TLG). Methods: Mouth breathing experiment and hypoxia tolerance experiment under atmospheric pressure with mice, experiment of dizziness of guinea pigs caused by chloroform, and stimulus ischemic vertigo of model rats caused by rotating in water maze experiment was used to investigate the anti-vertigo effect of TLG; The experiment of autonomic activities of mice and hypnosis experiment of mice with pentobarbital sodium was used to investigate the sedative hypnotic effect of TLG; The experiments of torsion body and hot plate of mice was used to investigate the analgesic effect of TLG; The experiments of swimming and regulating immune experiment was used to investigate the anti-fatigue and immune regulation effect of TLG. Results: TLG could promote the supplying of oxygen in the brain, significantly reduce the times of autonomic activities of mice, increase the number of sleeping mice at the subthreshold dose of sodium pentobarbital, shorten the sleep latency of mice with hreshold dose of sodium pentobarbital and prolong the sleep time, significantly increase mice body torsion reaction latency by the acetic acid and reduce the body torsion times, and increase the spleen thymus index, clearance coefficient and phagocytic index of mice. Conclusion: TLG has the effect of treating dizziness, forgetfulness, waist and knee fatigue weakness and so on.
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The sedative traditional Chinese medicine has a long history of clinical experience in treating insomnia. The main pharmacological effects of sedative agents are sedation, hypnosis, antianxiety and antidepression which might be related to certain neurotransmitters and cytokines and so on. This review summarized the mechanism of sedative traditional Chinese medicine and its active monomers based on neurotransmitters, including GABA, Glu, 5-HT, DA, NE and their metabolites 5-HIAA, HVA, DOPAC. The results showed that the most research about the sedative medicine at present was throught serotonergic and GABA ergic system. Study on Ziziphi Spinosae Semen was the most extensive, including its monomers, extracts and traditional Chinese patent medicines. It involved many sedative traditional Chinese medicine, such as Schisandrae Chinensis Fructus, Albiziae Flos, Polygalae Radix, Longan Arillus, Ganoderma, etc. It also systematically summarized the information which was useful for the further applications and research on sedative drugs and their active components.
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Insomnia was a common disease, which might be correlated with γ-aminobutyric acid A (GABAA) receptor mechanism, cytokine regulatory mechanism, excitatory amino acid mechanism and hydroxytryptamine (5-HT) receptor mechanism, but the correlations between these independent mechanisms and pathological characterization were still unclear. To further explore the effect of Banxia Houpo decoction on known or unknown biological pathways during treatment of insomnia, the metabonomics method based on ¹H-NMR was developed for detecting the significant changes in metabolomics after the administration with Banxia Houpo decoction in pentobarbital sodium-induced rat sleeping experiment. Serum and urine samples were analyzed by ¹H-NMR. Principal component analysis (PCA) was carried out for endogenous small molecule metabolites in urine and serum. H-NMR spectroscopies and relevant metabolites were found and identified by Simca-p 17.0 (Umet-rics, Umea, Sweden) and Chenomx NMR Suite 7.1 (Chenomx, Inc., Edmonton, Alberta, Canada) software. The result suggests that Banxia Houpo decoction group and indiplon group had significant differences. The load diagram showed the biggest variation metabolites and intergroup significant differences among 10 metabolic substances. According to the experiment, Banxia Houpo decoction group and indiplon group can prolonge the sleeping time of pentobarbital sodium-induced sprague-dawley rats, with a synergistic effect. The significant changes of these biomarkers indicated that the Banxia Houpo decoction could aid sleep by adjusting the content of glutamine, creatine phosphate, 2-oxoglutarate, and reducing the activity of brain nerves.
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Objective To explore the mechanism ofTiaozhong Huatan Anshen Mixture (THAM). Methods A total of 200 healthy Kunming mice were randomly and equally divided into first, second, third and fourth major groups. Each major group was further equally divided into blank group, control group and high, medium, low dose THAM groups. Each group was given an equal volume of NS, estazolam, or high, medium, or low dose THAM by gavage for 7 d. For the first major group, the changes in number of spontaneous activities after administration were evaluated. For the second major group, 60 min after administration, each group was given pentobarbital sodium (30 mg/kg body weight, minimum dose for all mice sleeping) by intraperitoneal injection, and the sleep time was recorded. For the third major group, 60 min after administration, each group was given pentobarbital sodium (15 mg/kg body weight, maximum dose for 90%-100% of all mice having righting reflex) by intraperitoneal injection. The number of mice falling asleep was recorded, and the sleep rate was calculated. For the fourth major group, mice were sacrificed after continuous administration 15 d. They were quickly removed brain tissue;homogenates were taken out in batches;5-HT and 5-HIAA levels in brain tissues were determined according to fluorescence spectrophotometric.Results Compared with the blank group, all treated groups had a reduced number of spontaneous activities, a shortened sleep latency, a prolonged sleep time, and an increased sleep rate after administration (P0.05). Compared with the blank group, brain 5-HT and 5-HIAA levels in all treated groups increased in mice (P<0.01,P<0.05), with the most significant changes seen in the high-dose THAM group (P<0.05).Conclusion THAM has a significant sedative-hypnotic effect. The mechanism may be related to increasing brain 5-HT synthesis and metabolism.
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This study was performed to investigate the sedative-hypnotic activity of gamma-aminobutyric acid (GABA)-enriched fermented marine organisms (FMO), including sea tangle (FST) and oyster (FO) by Lactobacillus brevis BJ20 (L. brevis BJ20). FST and FO were tested for their binding activity of the GABA(A)-benzodiazepine and 5-HT(2C) receptors, which are well-known molecular targets for sleep aids. We also measured the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of FST and FO. In GABA(A) and 5-HT(2C) receptor binding assays, FST displayed an effective concentration-dependent binding affinity to GABA(A) receptor, similar to the binding affinity to 5-HT(2C) receptor. FO exhibited higher affinity to 5-HT(2C) receptor, compared with the GABA(A) receptor. The oral administration of FST and FO produced a dose-dependent decrease in sleep latency and increase in sleep duration in pentobarbital-induced hypnosis. The data demonstrate that FST and FO possess sedative-hypnotic activity possibly by modulating GABA(A) and 5-HT(2C) receptors. We propose that FST and FO might be effective agents for treatment of insomnia.
Subject(s)
Animals , Mice , Administration, Oral , Aquatic Organisms , gamma-Aminobutyric Acid , Hypnosis , Levilactobacillus brevis , Ostreidae , Receptor, Serotonin, 5-HT2C , Receptors, GABA-A , Sleep Initiation and Maintenance DisordersABSTRACT
Background: Ficus carica Linn. is reported to possess variety of activities, but its potential in CNS disorders is still to be explored. Objective: The present study was carried out to evaluate the CNS depressant activity of aqueous acetonic extract of Ficus carica Linn on different models in mice. Materials and Methods: The aerial parts of the plant Ficus carica L. were extracted with aqueous acetone and the solvent was removed by rotary vacuum evaporator under reduced pressure. A crude extract was given orally and its effects were tested on ketamine-induced sleeping time, muscle-coordination, anxiety (elevated-plus maze and Staircase test), convulsions [maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures], and nociception. In addition, we determined the levels of neurotransmitters, norepinephrine (NE) and 5-hydroxytryptamine (5-HT). Results: Results from the experimental models tested showed: (1) a delay on onset and prolongation of sleep of ketamine-induced sleeping time; (2) signifi cant muscle relaxant activity; (3) a signifi cant attenuation in the anxiety-response (4) a delay in the onset of seizures and reduction in duration of seizures and mortality induced by MES and PTZ; (5) a reduction in the licking time in nociception test and (6) increased levels of NE and 5-HT. Conclusion: This suggests that Ficus carica L. exerts its CNS depressive effect by modulating the neurotransmitters NE and 5-HT in the brain.
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OBJECTIVE: To establish an HPLC-DAD method for the detection of midazolam, phenobarbital, estazolam, oxazepam, nitrazepam, alprazolam, clonazepam and diazepam illegally adulterated into traditional Chinese medicines and health foods. METHODS: An Alltima C18 column (4.6 mm × 250 mm, 5 μm) was used for the separation with 10 mmol · L-1 ammonium dihydro-gen phosphate (adjusted pH to 2.7 with H3PO4) - acetonitrile (65:35) or 10 mmol · L-1 ammonium dihydrogen phosphate (adjusted pH to 2.7 with H3PO4) - methanol (40:60) as the mobile phase at the flow rate of 0.5 mL · min-1. The detection wavelength was 220 nm. RESULTS: The method showed good linearity and sensitivity for the 8 compounds with all correlation coefficients (r) greater than 0.9997 and all LODs between 4.3 - 13.0 ng · mL-1; the spiked recoveries of low, middle and high levels ranged from 98.08% to 102.1%; the precisions were satisfactory with all RSDs lower than 1.58%; the stability within 12 h was acceptable with the RSDs of peak areas and retention times no more than 1.05% and 0.54%. In the test of 19 samples of different dosage forms, nitrazepam was found in two health foods. CONCLUSION: This method is fast, sensitive and propagable for the detection of 8 sedative hypnotics illegally adulterated into traditional Chinese medicines and health foods. Copyright 2012 by the Chinese Pharmaceutical Association.