We evaluate the sedative and hypnotic activities of the methanolic and aqueous extract of Lavandula officinalis L. on central nervous system (CNS). In this study, the effect of the methanolic and aqueous extracts of this plant was investigated in a battery of behavioural models in mice. Stems and flowers of Lavandula officinalis L. have several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including insomnia. The methanolic extract produced significant sedative effect at the doses of 200, 400, and 600 mg/kg (by oral route), compared to reference substance diazepam (DZP), and an hypnotic effect at the doses of 800 and 1000 mg/kg while the treatment of mice with the aqueous extract at the doses of 200 and 400 mg/kg via oral pathway significantly reduced in both the reestablishment time and number of head dips during the traction and hole-board tests. In conclusion, these results suggest that the methanolic and aqueous extracts of Lavandula officinalis possess potent sedative and hypnotic activities, which supported its therapeutic use for insomnia.
Asperugo procumbents L. has been used in Iranian traditional medicine for the refreshing, tranquillizing and mood elevating activities. The present study was undertaken to evaluate the antidepressant and sedative-hypnotic potential of acute administration of the hydroalcoholic extract of this plant in mice. Additionally, the effects of flumazenil on the hypnotic activity of the extracts were evaluated. None of the doses of the extract could significantly reduce immobility time in comparison with control group in antidepressant tests. In hypnotic test, 250 and 400 mg/kg dose ssign ificantly increased pentobarbital-induced sleeping time compared to vehicle. All of the doses of the extract significantly reduced the latency to sleep in comparison to the vehicle. Flumazenil reversed the augmented effects of extracts in pentobarbital-induced hypnotic test. The results of the present study indicate the low antidepressant and good sedative-hypnotic effects of the hydroalcoholic extract of Asperugo procumbens aerial parts in mice and that the central benzodiazepine receptors are involved in the sedative-hypnotic effects of this plant.
Depression; Asperugo procumbens L.; Forced swimming test; Tail suspension
Objectives To quantify and compare potential benefits (subjective reports of sleep variables) and risks (adverse events and morning-after psychomotor impairment) of short term treatment with sedative hypnotics in older people with insomnia.
Data sources Medline, Embase, the Cochrane clinical trials database, PubMed, and PsychLit, 1966 to 2003; bibliographies of published reviews and meta-analyses; manufacturers of newer sedative hypnotics (zaleplon, zolpidem, zopiclone) regarding unpublished studies.
Selection criteria Randomised controlled trials of any pharmacological treatment for insomnia for at least five consecutive nights in people aged 60 or over with insomnia and otherwise free of psychiatric or psychological disorders.
Results 24 studies (involving 2417 participants) with extractable data met inclusion and exclusion criteria. Sleep quality improved (effect size 0.14, P < 0.05), total sleep time increased (mean 25.2 minutes, P < 0.001), and the number of night time awakenings decreased (0.63, P < 0.001) with sedative use compared with placebo. Adverse events were more common with sedatives than with placebo: adverse cognitive events were 4.78 times more common (95% confidence interval 1.47 to 15.47, P < 0.01); adverse psychomotor events were 2.61 times more common (1.12 to 6.09, P > 0.05), and reports of daytime fatigue were 3.82 times more common (1.88 to 7.80, P < 0.001) in people using any sedative compared with placebo.
Conclusions Improvements in sleep with sedative use are statistically significant, but the magnitude of effect is small. The increased risk of adverse events is statistically significant and potentially clinically relevant in older people at risk of falls and cognitive impairment. In people over 60, the benefits of these drugs may not justify the increased risk, particularly if the patient has additional risk factors for cognitive or psychomotor adverse events.
Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed.
The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification.
Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities.
Plants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA.
Cholangiocarcinoma; Anticancer; Thai medicinal plants; Nude mouse xenograft model
The costs associated with alcohol abuse are staggering, therefore much effort has been put into developing new pharmacological strategies to decrease alcohol abuse. Recently, the nicotinic acetylcholine receptor (nAChR) partial agonist varenicline has been shown to decrease ethanol consumption in both humans and animal models.
We examined the effects of varenicline on the ataxic and sedative-hypnotic effects of ethanol. First, varenicline was administered prior to placement in a locomotor activity chamber to determine if varenicline influenced baseline locomotor activity. To determine the effect of nicotinic modulation on ethanol-induced motor incoordination, varenicline was administered 30 min prior to an acute ethanol injection and then mice were tested on the balance beam, dowel test or fixed-speed rotarod. To examine ethanol's sedative-hypnotic effects, varenicline was administered 30 min prior to 4 g/kg ethanol and the duration of loss of righting reflex (LORR) was measured.
Varenicline markedly reduced baseline locomotor activity in C57BL/6J mice. Varenicline increased ethanol-induced ataxia when measured on the balance beam and dowel test, but had no effect when measured on the fixed-speed rotarod. Pretreatment with varenicline increased the duration of LORR.
These data provide evidence that nAChRs may be involved in the ataxic and sedative effects of ethanol. It is possible that one mechanism which could contribute to the ability of varenicline to decrease ethanol consumption may be through increasing negative behavioral effects of alcohol.
Ethanol; Varenicline; Nicotinic Acetylcholine Receptors; Ataxia; Sedation
Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. Cytisus scoparius (CS) Link, (Family: Leguminosae), also called Sarothamnus scoparius, has been shown in invitro experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats.
60% methanolic extract of CS was quantified for phenolic content by Folin-Ciocalteau's method. Chronic unpredictable mild stress (CMS) was employed to induce stress in rats. CS (125 and 250 mg/kg, p.o) and diazepam (DZM) (2 mg/kg, p.o) was administered during the 21 day stress exposure period. Anxiolytic and antidepressant activities of CS were assessed in open field exploratory and behavioural despair paradigms, respectively. Plasma glucose and total lipids; endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT); non-enzymic-ascorbic acid and thiobarbituric acid reactive substances (TBARS) levels were measured in brain, kidneys and adrenals using standard protocols to assess the effect of CS.
Total phenolic content of CS was found to be 8.54 ± 0.16% w/w. CMS produced anxiogenic and depressive behaviour in experimental rats with metabolic disturbance. Significant decrease in SOD, CAT levels and increase in lipid peroxidation level was observed in stressed rats. CS administration for 21 days during stress exposure significantly increased the ambulatory behaviour and decreased the freezing time in open field behaviour. In behavioural despair test no significant alteration in the immobility period was observed. CS also improved SOD, CAT, and ascorbic acid level and controlled the lipid peroxidation in different tissues.
CS possesses anti-stress and moderate anxiolytic activity which may be due, in part, to its antioxidant effect that might warrant further studies.
Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE) and its active ingredient puerarin on alcoholism using rodent models.
Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR) assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR) subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH) levels in liver were measured.
FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models.
The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders.
Lactuca sativa (garden lettuce) is a popular salad herb. It has been in use in folk medicine since ancient times as both an appetite stimulant and as an aid to sleep. L. sativa seed oil (Sedan®) has demonstrated a pronounced sedative effect and potentiated the hypnotic effect of barbiturates in animal models. It also exhibited significant analgesic and anti-inflammatory activities. In this study, we evaluated the sedative and hypnotic effects of L. sativa in patients suffering from insomnia.
Sixty patients suffering from insomnia with or without anxiety were randomized to receive capsules containing L. sativa seed oil 1000 mg (n = 30) or placebo (n = 30). All patients were asked to complete a verbal questionnaire before the start of the trial and 1 week after starting treatment.
Improvements in the modified State-Trait Anxiety Inventory and the Sleep rating scale scores were significantly greater in patients receiving L. sativa seed oil compared with those on placebo (P < 0.05). No side effects were found to be attributable to L. sativa seed oil at the given dosage.
L. sativa seed oil was found to be a useful sleeping aid and may be a hazard-free line of treatment, especially in geriatric patients suffering from mild-to-moderate forms of anxiety and sleeping difficulties.
Lactuca sativa seed oil; insomnia; sleeping disorder; anxiety
Insomnia is a sleeping disorder characterised by persistent difficulty in falling asleep or staying asleep despite the opportunity. It is one of the burning problems all over the world. Statistics shows that 20% - 40% adults encounter insomnia problems during a year time. Allopathic hypnotic drugs are useful for short term treatment in Insomnia which is due to acute stage. Long term uses of certain classes of sedatives cause physical dependence and withdrawal symptoms also have a number of side effects. In the present era, patient prefers readymade, cost effective, easily palatable drugs with fewer side effects for their health problems. For the present clinical trial, Parsikayavanyadi Capsule consisting of Parasikayavani, Jatamamsimoola, triturated with juice of Sankhpushpi and Kushmanda, was formulated to evaluate its efficacy in the management of insomnia
Total 32 patients of newly diagnosed case of insomnia who were randomly divided in to two groups. In Group P.V (Parasikayavanyadi group), 20 patients were administered 5 capsules of Pariskvayanadi Churna of 500 mg each with a cup of warm milk at bed time for one month. In Group P.C (Placebo group), 12 patients were given Starch Capsules of 500 mg each with same Anupana and duration. Assessment was done considering the overall improvement of insomnia according to Pittsburgh insomnia rating Scale, improvement of associated complains of insomnia, relieving of negative emotions, improving of positive emotions, relieving of level of anxiety according to Hamilton Anxiety Rating Scale and relieving of level of depression according to Hamilton Depression Rating scale before and after one month of treatment period.
parasikayavanyadi capsule provided significant effect in the management of insomnia.
The study has revealed that parasikayavanyadi capsule provided significant effect in the management of insomnia in comparison to placebo.
Achyranthes aspera Linn., an indigenous herb, has been reported to have antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic, cardiotonic, analgesic anti-inflammatory, hypnotic, antifungal, antibacterial, and central antinociceptive activities.
This study was designed to evaluate depressant effects on central nervous system (CNS) and behavioral effects of ethanol extract of A. aspera (EEAA) and to find the phytochemical responsible for these activities.
Materials and Methods:
The pharmacological assays used to study CNS depressant effect in albino mice were rota rod and actophotometer performance test. Effects on behavioral activity were studied using open field test. The extract was given intraperitoneally (i.p.) at a dose of 400 mg/kg. Diazepam (2 mg/kg body weight i.p.) was used as standard.
Statistical Analysis Used:
Data were analyzed by using analysis of variance followed by Dunnett's test. P < 0.05 was considered significant.
Phytochemical screening revealed presence of triterpenoids, saponins, alkaloids (betaine, achyranthine), and steroids as major constituents. The result of this study reflected that EEAA (400 mg/kg i.p.) decreased locomotor activity, produced muscle relaxation, and showed anxiolytic activity.
EEAA exhibit CNS depressant and significant anxiolytic activity comparable to diazepam.
Achyranthes aspera; actophotometer; open field test; rota-rod
Insomnia is a common, often chronic medical disorder with significant medical and socioeconomic repercussions. However, unlike other medical conditions, there is intense debate as to whether the long-term treatment of insomnia is clinically appropriate. The perceived deleterious side effect of sedative-hypnotic medications may result in patients remaining untreated or undertreated. This review proposes that a more subtle approach needs to be taken in the management of patients with chronic insomnia and that long-term use of the newer sedative-hypnotics may be a feasible and effective treatment option when used in conjunction with thorough medical assessment and regular patient follow-up. This review discusses these issues and discusses the pros and cons of long-term sedative-hypnotic use.
insomnia; long-term use; hypnotics
An estimated one-third of the general population is affected by insomnia, and this number is increasing due to more stressful working conditions and the progressive aging of society. However, current treatment of insomnia with hypnotics, gamma-aminobutyric acid A (GABAA) receptor modulators, induces various side effects, including cognitive impairment, motor disturbance, dependence, tolerance, hangover, and rebound insomnia. Ramelteon (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin MT1/MT2 receptor agonist. Unlike the sedative hypnotics that target GABAA receptor complexes, ramelteon is a chronohypnotic that acts on the melatonin MT1 and MT2 receptors, which are primarily located in the suprachiasmatic nucleus, the body's “master clock.” As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades. Ramelteon has demonstrated sleep-promoting effects in clinical trials, and coupled with its favorable safety profile and lack of abuse potential or dependence, this chronohypnotic provides an important treatment option for insomnia.
Insomnia; Melatonin; MT1 receptor; MT2 receptor; Ramelteon; Suprachiasmatic nucleus (SCN); TAK-375
Iron is an essential nutrient for a number of cellular activities. However, excess cellular iron can be toxic by producing reactive oxygen species (ROS) such as superoxide anion (O2−) and hydroxyl radical (HO·) that damage proteins, lipids and DNA. Mutagenic and genotoxic end products of lipid peroxidation can induce the decline of mitochondrial respiration and are associated with various human ailments including aging, neurodegenerative disorders, cancer etc. Zingiber officinale Roscoe (ginger) is a widely used spice around the world. The protective effect of aqueous ethanol extract of Z. officinale against ROS-induced in vitro lipid peroxidation and DNA damage was evaluated in this study. The lipid peroxidation was induced by hydroxyl radical generated from Fenton’s reaction in rat liver and brain homogenates and mitochondrial fraction (isolated from rat liver). The DNA protection was evaluated using H2O2-induced changes in pBR-322 plasmid and Fenton reaction-induced DNA fragmentation in rat liver. The results indicated that Z. officinale significantly (P<0.001) protected the lipid peroxidation in all the tissue homogenate/mitochondria. The extract at 2 and 0.5 mg/ml could protect 92 % of the lipid peroxidation in brain homogenate and liver mitochondria respectively. The percent inhibition of lipid peroxidation at 1mg/ml of Z. officinale in the liver homogenate was 94 %. However, the extract could partially alleviate the DNA damage. The protective mechanism can be correlated to the radical scavenging property of Z. officinale. The results of the study suggest the possible nutraceutical role of Z. officinale against the oxidative stress induced human ailments.
Antioxidants; Nutraceutics; Reactive oxygen species; Zingiber officinale
Kupeelu (Strychnos nux-vomica Linn.) commonly known as nux vomica is a poisonous plant used extensively in various ayurvedic formulations, with great therapeutic significance. Ayurveda recommended the administration of Kupeelu only after purification in different media like cow's urine (Go mutra), cow's milk (Go dugdha), cow's ghee (Go ghrita), Kanji (sour gruel), and so on. Apart from the classical methods some other methods are also adopted by the traditional practitioners using castor oil (Eranda taila), ginger juice (Ardraka swarasa), in the purification of Kupeelu seeds. In the present study an attempt has been made to purify the seeds by performing two different methods (one classical and another traditional) using Kanji and Ardraka
swarasa as Shodhana media. This study reveals that both the methods studied reduce the strychnine and brucine contents in comparison to the raw seeds as determined by high performance thin layer chromatography (HPTLC). After purification in Kanji and Ardraka swarasa, the strychnine content was reduced by 39.25% and 67.82%, respectively, and the brucine content in the purified seeds was also found to have decreased by 17.60% and 40.06%, in comparison to the raw seeds.
Ardraka swarasa; brucine; kanji; kupeelu; shodhana; strychnine
Progesterone affects the function of the brain by multiple mechanisms. The physiological effects of progesterone are mediated by interaction of the hormone with progesterone receptors (PRs), which are widely expressed in the hypothalamus, hippocampus and limbic areas. The PR is composed of two protein isoforms, PR-A and PR-B, which are expressed from a single PR gene. In addition, progesterone influences neuronal activity through its conversion to allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of GABAA receptors. However, the role of PRs in the sedative-hypnotic action of neurosteroids is unclear. In this study, PR knockout (PRKO) mice were used as model to study the sedative-anesthetic actions of the progesterone-derived neurosteroid allopregnanolone and the non-competitive NMDA receptor antagonist ketamine. Mice were confirmed to be PR deficient by genotyping and immunohistochemistry of PR expression in the brain. Anesthetic potency was evaluated by the loss of the righting reflex paradigm. Allopregnanolone induced anesthetic activity was similar in PRKO mice and their wild-type littermates, suggesting that PRs are not involved in the anesthetic response to allopregnanolone. However, the non-competitive NMDA receptor antagonist ketamine has significantly reduced anesthetic potency in PRKO mice, suggesting a possible developmental plasticity of glutamate receptors. There was no marked gender-related difference to ketamine response in both genotypes. In conclusion, these results suggest that the neurosteroid allopregnanolone and ketamine produce differential anesthetic response in mice lacking PRs.
Allopregnanolone; Anesthesia; Neurosteroid; Progesterone receptor
Sedative-hypnotic CNS depressant drugs are widely prescribed to treat a variety of disorders, and are abused for their sedative and euphoric effects. Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains their use/abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates depressant dependence, models for specific factors, like withdrawal, are useful for identifying potential neural determinants of liability in humans. Recent analyses implicate the caudolateral substantia nigra pars reticulata (clSNr) in withdrawal following acute and repeated ethanol exposures in mice, but did not assess its impact on withdrawal from other sedative-hypnotics or whether intrinsic neurons or fibers of passage are involved. Here, we demonstrate that bilateral chemical (ibotenic acid) lesions of the clSNr attenuate barbiturate (pentobarbital) and ethanol withdrawal. Chemical lesions did not affect convulsions in response to pentylenetetrazol, which blocks GABAA receptor-mediated transmission. Our results demonstrate that the clSNr nucleus itself rather than fibers of passage is crucial to its effects on barbiturate and ethanol withdrawal. These findings support suggest that clSNr could be one of the shared neural substrates mediating withdrawal from sedative-hypnotic drugs.
seizure; sedative-hypnotic; lesion; ibotenic acid; convulsion
We investigated the antianxiety and sedative effects of the essential oil of Ducrosia anethifolia. Boiss. (Apiaceae).
We used elevated plus maze, spontaneous motor activity and ketamine‐induced sleep tests in mice. In addition, the essential oil was analyzed by GC/MS. Twenty compounds were identified, and n‐decanal (70.1%) and alpha‐pinene (12.4%) constituted the major components.
In elevated plus maze, Ducrosia anethifolia essential oil at doses of 25–200 mg/kg increased the percentage of open arm time and entries. Unlike diazepam, ducrosia anethifolia essential oil could not suppress spontaneous motor activity and did not alter ketamine‐induced sleep parameters. These results are indicative of antianxiety effect of Ducrosia anethifolia essential oil without sedative effect.
Apiaceae; diazepam; elevated plus‐maze; ketamine; spontaneous motor activity
The successful use of conscious sedation in patients physically dependent on centrally acting drugs is problematic for the dental anesthesiologist because of the concomitant development of tolerance to standard sedative agents. Dosage requirements necessary to adequately sedate these patients are often higher than recommended and carry an increased risk of drug overdose. The following report summarizes our experience with 18 drug-dependent patients in whom hypnosis was employed in conjunction with a standard sedation regimen. Attempts to complete various dental procedures while employing sedation alone on these patients had previously failed. All patients exhibited highly fearful or phobic behavior toward dental treatment as assessed by the Corah Dental Anxiety Scale. If an intravenous sedative regimen (midazolam or diazepam plus methohexital) was employed, hypnotic induction preceded the administration of the sedative drugs. If an intramuscular sedative regimen was employed (meperidine plus promethazine), the hypnotic induction took place after drug administration. With the combined hypno-sedative approach, treatment outcomes were judged to be good or excellent in 11 of 18 patients. Interestingly, in five of seven patients for whom the treatment outcome was rated poor or fair, the possibility of tolerance or cross-tolerance existed between a drug being abused and the sedative regimen. In contrast, this possibility existed in only 1 of 11 patients with good or excellent treatment outcomes. We conclude that hypnosis can augment the effects of sedation in this patient population. However, it is also important to choose a sedative regimen where tolerance is unlikely to exist.
OBJECTIVE: Mental distress may entail increased risk of hip fracture, but it is uncertain whether the effect consists solely of an indirect effect through use of medication, or whether it is also mediated through other mechanism. The purpose of this study was to examine the association between mental distress and risk of hip fracture in women, adjusted for medication (that is, use of tranquillisers/sedatives or hypnotics). DESIGN: A three year follow up of hip fracture was conducted on 18,612 women, consisting of 92.5% of all women aged 50 years or older in a Norwegian county. Three hundred and twenty nine suffered a hip fracture. A mental distress index was based on questions about life dissatisfaction, nervousness, loneliness, sleep disorders, troubled and uneasy feelings, depression and impairment attributable to psychological complaints. Relative risk with 95% confidence intervals (CI) of hip fracture with respect to mental distress were controlled for medication, age, body mass index (BMI), smoking, physical inactivity, and physical illness by means of Cox regression. RESULTS: The 10% of women with the highest mental distress had more than twofold increased risk of hip fracture compared with the 10% of women with the lowest mental distress, after adjustment for age and medication. The relative risk was 1.95 (95% CI 1.2, 3.3) after additional control for BMI, smoking, physical inactivity, and physical illness. The relative risk of hip fracture for daily users of medication compared with never users was 2.1 (95% CI 1.6, 2.9). After adjusting for mental distress it was 1.5 (95% CI 1.0, 2.2). CONCLUSIONS: Risk of hip fracture was positively related to mental distress, also after adjustment for medication use. The effect of tranquillisers/sedatives or hypnotics on hip fracture risk may be overestimated in studies with no adjustments for mental distress.
Of the patients in an industrial general practice 1.3% required hypnotic drugs regularly. They were predominantly in the older age groups (mean 62.7 years), with an excess of widows. Only 0.02% were severely dependent; the remainder were mildly so, though they had been taking hypnotics for long periods (mean 5.6 years). There were three main original indications for hypnotics—namely, medical (pain), psychiatric, and onset insomnia in anxious personality disorder. One-fifth of the patients first took hypnotics while in hospital. The group as a whole manifested a high degree of abnormal psychological disposition.
It is suggested that many patients who take hypnotics regularly may be placebo reactors, and a more critical attitude to hypnotic prescribing is required both in hospital and in general practice.
Interaction with the gamma-aminobutyric-acid-type-A (GABAA) receptors is recognized as an important component of the mechanism of propofol, a sedative-hypnotic drug commonly used as anesthetic. However the contribution of GABAA receptors to the central nervous system suppression is still not well understood, especially in the thalamocortical network. In the present study, we investigated if intracerebral injection of bicuculline (a GABAA receptor antagonist) into the thalamus ventral posteromedial nucleus (VPM, a thalamus specific relay nuclei that innervated S1 mostly) could reverse propofol-induced cortical suppression, through recording the changes of both spontaneous and somatosensory neural activities in rat’s somatosensory cortex (S1). We found that after injection of bicuculline into VPM, significant increase of neural activities were observed in all bands of local field potentials (total band, 182±6%), while the amplitude of all components in somatosensory evoked potentials were also increased (negative, 121±9% and positive, 124±6%).These data support that the potentiation of GABAA receptor-mediated synaptic inhibition in a thalamic specific relay system seems to play a crucial role in propofol-induced cortical suppression in the somatosensory cortex of rats.
To investigate the proposed synergistic teratogenic effect of use of selective serotonin receptor inhibitors (SSRI) together with sedatives or hypnotics, primarily benzodiazepines, during pregnancy.
Cohort study of congenital malformations after maternal use of SSRI, sedatives/hypnotics or the combination of the two drug categories.
Swedish national health registers.
A total of 10 511 infants born of women who had used SSRI drugs but no other central nervous system (CNS)-active drug, 1000 infants born of women who had used benzodiazepines and no other CNS-active drug, and 406 infants whose mothers had used both SSRI and benzodiazepines but no other CNS-active drug.
None of the three groups showed a higher risk for any relatively severe congenital malformation or any cardiac defect when comparison was made with the general population risk (adjusted risk ratio (RR) for the combination of SSRI and benzodiazepines and a relatively severe malformation=1.17 (95% CI 0.70 to 1.73). Similar results were obtained for the combination of SSRI with other sedative/hypnotic drugs.
The previously stated increased risk associated with the combined use of these drug categories, notably for a cardiac defect, could not be replicated.
In order to explore how the choice of different study designs could influence the risk estimates, a case–crossover and case–time–control study were carried out and their outcomes were compared with those of a traditional case–control study design that evaluated the association between the exposure to psychotropic medications and the risk of having a motor vehicle accident (MVA). A record-linkage database availing data for 3,786 cases and 18,089 controls during the period 2000–2007 was used. The study designs (i.e., case–crossover and case–time–control) were derived from published literature, and the following psychotropic medicines were examined: antipsychotics, anxiolytics, hypnotics and sedatives, and antidepressants, stratified in the two groups selective serotonin reuptake inhibitors (SSRIs) and other antidepressants. Moreover, in order to further investigate the effects of frequency of psychoactive medication exposure on the outcomes of the case–crossover analysis, the data were also stratified by the number of defined daily doses (DDDs) and days of medication use in the 12 months before the motor vehicle accident. Three-thousand seven-hundred fifty-two cases were included in this second part of the case–crossover analysis. The case–crossover design did not show any statistically significant association between psychotropic medication exposure and MVA risk [e.g., SSRIs—Adj. OR = 1.00 (95 % CI: 0.69–1.46); Anxiolytics—Adj. OR = 0.95 (95 % CI: 0.68–1.31)]. The case–time–control design only showed a borderline statistically significant increased traffic accident risk in SSRI users [Adj. OR = 1.16 (95 % CI: 1.01–1.34)]. With respect to the stratifications by the number of DDDs and days of medication use, the analyses showed no increased traffic accident risk associated with the exposure to the selected medication groups [e.g., SSRIs, <20 DDDs—Adj. OR = 0.65 (95 % CI: 0.11–3.87); SSRIs, 16–150 days—Adj. OR = 0.55 (95 % CI: 0.24–1.24)]. In contrast to the above-mentioned results, our recent case–control study found a statistically significant association between traffic accident risk and exposure to anxiolytics [Adj. OR = 1.54 (95 % CI: 1.11–2.15)], and SSRIs [Adj. OR = 2.03 (95 % CI: 1.31–3.14)]. Case–crossover and case–time–control analyses produced different results than those of our recent case–control study (i.e., case–crossover and case–time–control analyses did not show any statistically significant association whereas the case–control analysis showed an increased traffic accident risk in anxiolytic and SSRI users). These divergent results can probably be explained by the differences in the study designs. Given that the case–crossover design is only appropriate for short-term exposures and the case–time–control design is an elaboration of this latter, it can be concluded that, probably, these two approaches are not the most suitable ones to investigate the relation between MVA risk and psychotropic medications, which, on the contrary, are often use chronically.
Psychotropic medications; Road traffic accidents; Case–crossover study; Case–time–control study; Case–control study; Pharmacoepidemiology
The seeds of Ziziphus mauritiana Lam. have been traditionally used for treatment of various complications including insomnia and anxiety. They are popularly used as sedative and hypnotic drugs in China, Korea, Myanmar, Vietnam, and other Asian countries. However, no scientific proof on hypnotic activity of Z. mauritiana seeds (ZMS) was reported. In this study, the hypnotic activity of 50% ethanolic extract from ZMS was observed on the loss of righting reflex in mice using pentobarbital-induced sleep mice method. The contents of total phenolics and total flavonoids in the extract were also determined. The results showed that the 50% ethanolic extract from ZMS contained total phenolics 27.62 ± 1.43 mg gallic acid equivalent (GAE)/g extract and total flavonoids 0.74 ± 0.03 mg quercetin equivalent (QE)/g extract. Oral administration of the extract at the dose of 200 mg/kg significantly increased the sleeping time in mice intraperitoneally administered with sodium pentobarbital (50 mg/kg body weight). These results supported the traditional use of ZMS for the treatment of insomnia. The seeds of Z. mauritiana should be further developed as an alternative sedative and/or hypnotic product.
Mikania scandens (L.) Willd. (Asteraceae), known as climbing hemp weed in English, is a herbaceous climbing vine grown as a weed throughout the plains of the Indian subcontinent. The present study evaluated some neuropharmacological properties of hydroalcoholic extract of aerial parts from M. scandens (HAMS) in experimental animal models. HAMS (at 250 and 500 mg/kg body weight, i.p.) was evaluated for central antinociceptive activity by tail flick method. Locomotor depressant activity was measured by means of an actophotometer. Skeletal muscle relaxant effect was evaluated by using rotarod apparatus and sedative potentiating property by phenobarbitone-induced sleep potentiation study. The results of the present study revealed significant (P<0.001) and dose-dependent central antinociceptive, locomotor depressant, muscle relaxant, and sedative potentiating effects of HAMS, demonstrating its depressant action on the central nervous system (CNS). From the present study, it can be concluded that the aerial parts of M. scandens possessed prominent depressant action on the CNS, as manifested by the important neuropharmacological properties in mice.
Central nervous system depressant; locomotor; muscle relaxant; phenobarbitone