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espanolLas tecnicas de anestesia general se emplean en funcion de signos clinicos y tienden a presentar eventos en donde si no se aplica la anestesia necesaria, el paciente puede estar consciente y recordar eventos de una cirugia o puede que se aplique un exceso de anestesia y el paciente tarde en lograr la recuperacion. En tal sentido, el indice biespectral es una escala de medicion que mide la actividad electrica en el cerebro por medio de un monitor que brinda informacion al anestesista sobre la cantidad de anestesia que debe administrar al paciente. El indice biespectral (BIS) es un parametro de electroencefalograma recien procesado que se desarrollo especificamente para medir los efectos hipnoticos de la anestesia. Los resultados de los estudios realizados con voluntarios demuestran que el BIS se correlaciona bien con las evaluaciones clinicas de la sedacion inducida por farmacos hipnoticos sedantes. De acuerdo con las investigaciones y estudios, la monitorizacion BIS permite una mejor titulacion de la anestesia, lo que resulta en un menor uso de farmacos hipnoticos y una mejor recuperacion. Los datos sugieren que la titulacion de anestesicos mejorada con BIS proporciona suficientes beneficios clinicos y economicos para justificar su uso rutinario. Mediante el desarrollo de la investigacion, se resume el desarrollo clinico y la validacion de BIS y describe como se puede utilizar la monitorizacion de BIS para mejorar los resultados anestesicos. EnglishGeneral anesthesia techniques will be implemented in the function of clinical signals and present events in this area and will not require the need for anesthesia, the patient can be informed and record events of the brain or he can apply an-esthesia and the patient will to recover the recovery. In this regard, the indicative index is a scale of measurement that measures electrical activity in the middle of a monitor that provides information to the anesthetic about the amount of anes-thesia that must be administered to patients. The bispectral index (BIS) is an electroencephalogram parameter processed that is specifically designed to measure the hypnotic effects of anesthesia. The results of the studies carried out with the voluntary demonstrations that the BIS correlates well with the clinical evaluations of the sedation induced by sedative hypnotics. In order to investigate and study investigations, BIS monitoring allows a better title of anesthesia, which results in a use of hypnotic pharmacies and a better recovery. The data suggest that the anesthetic titration will be improved with a BIS proportion of sufficient clinical and economic benefits to justify its routine use. As a result of the development of the investigation, a summary of the clinical development and validation of the BIS and how it is possible to use the monitoring of the BIS to improve the anesthetic results.

Daphne giraldii Nitsche., a member of the genus Daphne (Thymelaeaceae), is a deciduous shrub with mild toxicity. Its rhizome bark, generally called 'Zushima' in Chinese, has many medicinal folkloric uses and good therapeutic effects. Previous studies investigating the chemical constituents and pharmacological activities of D. giraldii have focused on several major classes of compounds, such as coumarins, lignans and flavonoids, especially the interesting enantiomeric flavans. Extracts and pure compounds of D. giraldii were found to possess anti-inflammatory, anti-nociceptive, cytotoxicity, antimalarial, immunomodulating, sedative and hypnotic effects. They have also been reported to influence the cardiovascular functions and blood activities. This comprehensive review will describe the advances in the phytochemistry, pharmacology, medicinal uses and clinical applications of D. giraldii and its formulations covering the literature published from 1970 to 2018. Almost half of the reviewed studies were originally published in non-English languages (mainly in Chinese). Collectively, the aim of this article is to open new avenues for further in-depth pharmacological studies on D. giraldii.

As a well-known traditional Chinese medicine, Ziziphi Spinosae Semen has been used for treating anxiety and insomnia for a long time. Spinosin, the main active C-glycoside flavonoid in Ziziphi Spinosae Semen, has attracted much attention because of its many pharmacological activities including strong hypnotic effects, anxiolytic-like effects, and so on. In the present work, high-purity spinosin was separated from Ziziphi Spinosae Semen using the HPD-300 resin followed by preparative high-performance liquid chromatography. The adsorption kinetics curve of spinosin on the HPD-300 resin was studied and fitted well by the pseudo-second-order equation. The adsorption isotherms were also constructed and low temperature favored the adsorption reaction. The separation parameters were optimized using dynamic adsorption and desorption tests. After a one-run treatment with HPD-300 resin, the concentration of spinosin increased 11.8-fold from 0.99 to 11.7% with a recovery yield of 80.4%. Furthermore, the purity of spinosin could surpass above 98% after separation by preparative high-performance liquid chromatography and recrystallization with a recovery yield of 72.6%. The developed method was effective and suitable for the large-scale preparation of spinosin. Moreover, it was confirmed that HPD-300 resin could enable good selection for the enrichment of flavonoids from different plants.

Pinelliae Rhizoma Praeparatum Cum Alumine(PRPCA) is useful for eliminating dampness and phlegm in clinical settings, targeting the main mechanisms of insomnia as defined in traditional Chinese medicine. However, little is known regarding the sedative and hypnotic effects of PRPCA. In the present study, we examined the sedative effects of PRPCA via a locomotor activity test and aimed to determine the most appropriate concentration of PRPCA for achieving these effects. The strongest sedative effects were observed at a PRPCA concentration of 0.45 g/ml. In addition, we investigated the hypnotic effects of PRPCA and its role in promoting sleep via sleep monitoring and vigilance state analysis. PRPCA increased rapid eye movement (REM) sleep and non-REM (NREM) sleep while decreasing wakefulness. In addition, PRPCA decreased the number of bouts of wakefulness (16–32 s and 32–64 s) and increased the number of bouts of NREM sleep (128–256 s). Furthermore, we identified a total of 32 component compounds via chromatography and mass spectrometry. Hence, the current work provides valuable information regarding the sedative and hypnotic effects of PRPCA and its regulatory mechanisms in promoting sleep.

The present study aims to assess the anxiolytic and hypnotic activity of ethanolic extract of Cocculus laurifolius leaf in mice. Anxiolytic activity was observed using behavioral paradigms while hypnotic activity was assessed by sodium pentobarbital induced hypnosis in mice. Animals were treated with the extract at dose 200 and 400 mg/kg orally for 30 days. Anxiolytic and hypnotic effect were observed on day 1, 7, 15 and 30 of treatment. Significant increase in the number of entries and time spent in open arm were observed in elevated plus maze. Similar results were observed in light/dark, open field and hole board test. The anxiolytic effect was substantially greater at dose 200 mg/kg in comparison to dose 400 mg/kg. Minimal hypnotic activity was observed with decrease in onset and prolongation in duration of sleep at dose 400 mg/kg, while dose 200 mg/kg did not produce any hypnotic effect. These results showed that the ethanolic extract of C. laurifolius leaf might have potential anxiolytic and hypnotic activity in mice.

4-Hydroxybenzyl alcohol (HBA), one of the characteristic active components of Gastrodia elata, exhibits obvious effects on the human central nervous system. In order to acquire compounds with superior bioactivity, 10 derivatives of HBA were synthesized from HBA and carboxylic acids. The sedative effects of the 10 HBA derivatives were evaluated using a spontaneous locomotor activity test (SLT) in mice, and their hypnotic effects were determined to be synergistic with pentobarbital-induced sleep. The results showed that 4-hydroxybenzyl alcohol 3-furancarboxylic acid diester (2FHBA, 10 mg kg−1) exhibited the strongest sedative–hypnotic activity among HBA and its derivatives, and 2FHBA could reverse the insomnia caused by p-chlorophenylalanine (pCPA), flumazenil (FLU) and thiosemicarbazide (TSC). Meanwhile, 2FHBA and 5-hydroxytryptophan (5-HTP) showed a synergistic effect. The results suggested that 2FHBA might be a potential agent against insomnia, which might be mediated by the serotonergic and GABAergic systems.

Amygdalus communis L. (almond) has been traditionally used as a natural medicine in the treatment of various diseases. The present research studied the sedative and hypnotic effects of the aqueous fraction of seeds of almond in rats. In order to investigate these effects, a combination of behavioral methods (open field test and loss of righting reflex test) as well as quantitative and analytic methods (EEG and EMG) were applied. The results of the open field test showed that a dose of 400 mg/kg of the almond extract significantly inhibited the locomotion activity of rats compared to normal. The results also illustrated that the almond extract affected pentobarbital-induced sleep through increasing the number of fallings asleep and prolongation of sleeping time. Analysis of EEG recordings of the animals which had received the same dose of the almond extract as the open field test demonstrated marked changes in the animals' sleep architecture. Significant prolongation of total sleeping time as well as significant increase in NREM sleep were the main observed changes compared to the normal condition. These results suggest that the aqueous extract of almond has significant sedative and hypnotic effects, which may support its therapeutic use for insomnia.

The chick has a practical advantage in the screening process in that chicks require only small quantities of drugs. The chick separation stress paradigm has traditionally been recognized as a valid form of anxiolytic screening. Further, chick behavior involving standing motionless with eyes closed or sitting motionless with head drooped is nearly always associated with electrophysiological sleep. When centrally administered, some DNA-encoded L-α-amino acids, as well as some DNA-non-encoded amino acids, such as metabolites of L-α-amino acids, D-amino acid and β-amino acid, have shown sedative and/or hypnotic effects in chicks. The effects of some of these amino acids have subsequently been confirmed in humans. In conclusion, the chick model is convenient and useful for screening central functions of amino acids and their metabolites for hypnosis and sedation.

The objective of our work is to make a pharmacological study of molecules derived from 4-phenyl-1,5-benzodiazepin-2-one carrying long chains so that they have a structure similar to surfactants, with the benzodiazepine as a hydrophilic head and a carbon chain as a hydrophobic tail. First, we studied the acute toxicity of the above mentioned 4-phenyl-1,5-benzodiazepin-2-one derivatives. This study was conducted according to OECD 423 guidelines in female mice and revealed that these compounds are nontoxic. We then assessed the psychotropic effects of our products on the central nervous system (CNS). The results obtained show that 4-phenyl-1,5-benzodiazepin-2-one has no sedative effect at therapeutic doses of 100 and 200 mg/kg. On the other hand, its long-chain derivatives possess them. Moreover, all these products have no cataleptic and hypnotic effects at the doses studied. But at 100 mg/kg, these compounds all have the ability to significantly prolong the hypnotic effect of thiopental sodium.

Lactuca sativa Linn. (or lettuce) is a well known plant worldwide due to its use in the preparation of salad, soup, and vegetable curries. This plant also has excellent medicinal properties. Lettuce is cultivated worldwide, and is one of the most consumed green leafy vegetables in the raw form for its taste and high nutritive value. It is regarded as an important source of phytonutrients. It is characterized by considerable morphological and genetic variations. This leaf vegetable was first cultivated by the Egyptians. Today, it is produced all over the world and is used in forensic medicine for many ailments including pain, stomach problems and inflammation, and urinary tract infections. Different studies provided the scientific evidence of its pharmacological potential including antimicrobial, antioxidant, neuroprotective, and hypnotic effects. The chemical composition of the plant revealed the presence of different classes of secondary metabolites, such as terpenoids, flavonoids, and phenols which should be responsible for its biological activities. The plant also contains essential elements, such as vitamins as well as minerals and organic substances.

Jujuboside A (JuA) is a representative saponin with significant sedative and hypnotic effects. Up to now, there were many arguments on its metabolic mechanism. In this study, a high performance liquid chromatography-tandem mass spectrometry (MS/MS) method was developed for investigating the degradation characteristics of JuA incubated with rat feces. With the method, the degradation kinetics of JuA was studied. The results showed JuA decomposed rapidly. It could decompose nearly 100% in only 4–6 h. The degradation regularity was consistent with the first dynamic process. In addition, seven metabolites were determined and identified to be the serial hydrolysis products of JuA. The results revealed that gastrointestinal microbiota played an indispensable role in the metabolic process of JuA. JuA may be a supplier of sugars under the hydrolysis effect induced by the bacterial enzymes. At the same time, its aglycone was produced as a by-product, which could be easier to be absorbed into the body to perform it...

Schisandra has been used to treat insomnia for hundreds of years in China. This study was aimed at proving the contribution of Schisantherin A (STA), the most abundant component in Schisandra, on s...

Aim. To complete the computer prediction of possible spectrum of biological activity of simple amides of 2-oxyindolin-3-glyoxylic acid derivatives and to test their anxiolytic activity in experiment. Methods. The prediction of possible spectrum of biological activity of simple amides of 2-oxyindolin-3-glyoxylic acid derivatives was performed using PASS (Prediction of Activity Spectra for Substances) software. The experimental part was performed on 140 adult rats of both sexes. Animals were distributed to subgroups (n=10 in each subgroup) according to age and gender. Experimental screening for anxiolytic action was performed using the Vogel’s «conflict situation» method. Results. 12 compounds highly potential for anxiolytic activity were selected after the computer prediction. Glutamate, serotonin, aspartate receptors blockade, gamma-aminobutyric acid (GABA)-receptors stimulation and depression of GABA-aminotransferase were in the list of possible mechanisms of action. Along with anxiolytic activity anticonvulsive, antipsychotic, antihypoxic and hypnotic effects were predicted. During the Vogel’s «conflict situation» test, 2-Hydro-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide, 2-Hydro-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-N-phenyl-acetamide and N-[(2-Oxo-1,2-dihydro-indol-3-ylidene)-phenethylcarbamoyl-methyl]-benzamide had significantly decreased the latent time for taking water from drinking place. At the same time, 2-Hydro-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide, 2-Hydro-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-N-phenyl-acetamide, N-[(2-Oxo-1,2-dihydro-indol-3-ylidene)-phenethylcarbamoyl-methyl]-benzamide and 3-Hydroxy-3-(2-oxo-cyclohexylmethyl)-1-piperidin-1-ylmethyl-1,3-dihydro-indol-2-one compounds had significantly increased the number of punished attempts for getting water, assuming anxiolytic activity. Among 2-oxyindolin simple amides derivatives 2-Hydro-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide had the strongest anxiolytic effect in test with punished behavior. Conclusion. Computer prediction of 2-oxyindolin-3-glyoxylic acid derivatives anxiolytic effect was confirmed experimentally.

The purpose of this study was to evaluate the effects of astragalin on the central nervous system. Astragalin is a monomeric compound found in the leaves of Eucommia ulmoides using a system solvent method. In the experiments, astragalin showed significant effects on mice, including reduced spontaneous activity, increased sleep ratio, shortened sleep latency and lengthened sleep time with a subthreshold or superthreshold dose of pentobarbital sodium. In addition, astragalin effectively reduced the convulsion rate and prolonged convulsion latency. These findings confirmed that astragalin had excellent sedative and hypnotic effects and has potential to be commercialised as a novel nutraceutical agent to promote calming and improve central nervous system-associated pathologies.

Background Detection of mid-latency auditory evoked potentials (MLAEPs) is a technology to monitor central nervous structures. As seen in adults and children, general anaesthesia influences the MLAEP latencies. MLAEP detection seems to be a promising tool to assess different levels of anaesthesia depth in adults and children. Methods MLAEPs were recorded in 10 infants (2 months–3 yr), 12 schoolchildren (6–14 yr), and 10 elderly (75–89 yr) under general anaesthesia with increasing concentrations of sevoflurane at steady state. In addition, MLAEPs were detected before and after the application of sufentanil. Results At all different ages, MLAEP latencies increased significantly with higher volume percentages of sevoflurane. These results were also detectable when MAC values of sevoflurane were compared with MLAEP peaks. An age-dependent effect could be displayed as elderly people need lower absolute sevoflurane concentrations to achieve the same MLAEP peak increase. Overall, the application of sufentanil under steady-state sevoflurane application at 1 MAC did not importantly affect the MLAEP latencies. Conclusions MLAEP latencies increase at the influence of sevoflurane in a dose-dependent manner and in relation to age. These results imply that MLAEP detection is a reasonable tool for monitoring hypnotic effects at all ages. Further studies are required to standardize MLAEP alterations related to effects of medication used for general anaesthesia at all different ages.

IntroductionQuinine, is an anti-malarial drug that specifically blocks connexin 36 at gap junction channels.ObjectiveQuinine has suppressed ictal epileptiform activity in vitro without decreasing neuronal excitability.AimWe considered the possible anticonvulsant effects of quinine in the pentylenetetrazole (PTZ) model of seizure.MethodsIn five groups, the mice were given quinine at the doses of 20, 30, 40, 50, or 60 mg/kg 30 min before the administration of PTZ (90 mg/kg). Two groups were injected with diazepam, the positive control (0.5, 1 mg/kg) and one group, the control group, was injected with saline + Tween 80 before the administration of PTZ. The onset of a general clonus was used as the endpoint. The general clonus was characterized by forelimb clonus followed by full clonus of the body.ResultsIn the PTZ model, quinine at the dose of 60 mg/kg increased the latency of seizure. However, quinine at 40-60 mg/kg decreased the duration of seizure, dose dependently.ConclusionThe present study provides evidence for anticonvulsant activity of quinine in the generalized clonic seizure of PTZ model. As a result of these finding, we suggest that gap junctions represent an appropriate target for the development of drugs aimed at decreasing epileptiform synchronization and preventing epileptogenesis.

Mercury is a major toxic metal ranking top in the Toxic Substances List. Cinnabar (contains mercury sulfide) has been used in traditional medicines for thousands years as an ingredient in various remedies, and 40 cinnabar-containing traditional medicines are still used today. Little is known about toxicology profiles or toxicokinetics of cinnabar and cinnabar-containing traditional medicines, and the high mercury content in these Chinese medicines raises justifiably escalations of public concern. This minireview searched the available database of cinnabar, compared cinnabar with common mercurials, such as mercury vapor, inorganic mercury, and organic mercury, and discusses differences in their bioavailability, disposition, and toxicity. The analysis showed that cinnabar is insoluble and poorly absorbed from the gastrointestinal tract. Absorbed mercury from cinnabar is mainly accumulated in kidney, resembling the disposition pattern of inorganic mercury. Heating cinnabar results in release of mercury vapor, which in turn can produce toxicity similar to inhalation of these vapors. The doses of cinnabar required to produce neurotoxicity are thousands 1000 times higher than methyl mercury. Following long-term use of cinnabar, renal dysfunction may occur. Dimercaprol and succimer are effective chelation therapies for general mercury intoxication including cinnabar. Pharmacology studies of cinnabar suggest sedative and hypnotic effects, but the therapeutic basis of cinnabar is still not clear. In summary, cinnabar is chemically inert with a relatively low toxic potential when taken orally. In risk assessment, cinnabar is less toxic than many other forms of mercury, but the rationale for its inclusion in traditional Chinese medicines remains to be fully justified.

Summary Objective: We assessed the hypnotic effects of and patient satisfaction with three types of hypnotics prescribed empirically: ultra-short-acting (US-a), short-acting (S-a), and intermediate- and long-acting (IL-a) agents. Methods: We studied 310 insomniac patients (age 60·5 ± 15·0 years) treated with US-a (n = 124), S-a (n = 149) or IL-a (n = 37) agents. Patients were interviewed to evaluate individual satisfaction and drug efficacy. Efficacy, as assessed by total sleep time (TST) and sleep latency time (SLT), was compared between satisfied and dissatisfied patient groups. Nocturnal awaking curve for each hypnotic was used for comparing the effects between satisfied and dissatisfied patient groups in each type of hypnotics. Results: Thirty-two patients (25·8%) were dissatisfied with US-a, 35 (23·5%) with S-a and 11 (29·7%) with IL-a. TST differed significantly between satisfied and dissatisfied groups: 424 ± 88 vs. 345 ± 101 min for US-a (P

In the central nervous system, beta-alanine is thought to act as an inhibitory neurotransmitter, but the role or precise mechanism of beta-alanine in the brain has not been clearly defined. beta-Alanine is found in high levels in the chicken brain as a component of the dipeptides carnosine (beta-alanyl-L-histidine) and anserine, or as a free amino acid. We focused on the position of beta-alanine, i.e., at the carboxyl terminus. In Experiment 1, the central effects of glycyl-beta-alanine, L-histidyl-beta-alanine and L-valyl-beta-alanine were compared with a saline control in chicks. L-Histidyl-beta-alanine significantly induced sedative and hypnotic effects. In Experiment 2, the effects of carnosine, its reverse (L-histidyl-beta-alanine), and their combination were investigated. Central carnosine-induced hyperactivity while reverse carnosine-induced hypoactivity, and the behaviors were intermediate following the combination of the two peptides. Finally, the central effect of reverse carnosine was compared with beta-alanine alone and L-seryl-beta-alanine in Experiment 3. Reverse carnosine showed similar effects to beta-alanine. In conclusion, L-histidyl-beta-alanine not only has the reverse structure of carnosine, but also reverse function. Thus, we propose to name reverse carnosine (L-histidyl-beta-alanine) rev-carnosine.

L-arginine participates in many important and diverse biochemical reactions associated with the normal physiology of the organism. In the present study, we investigated the effect of central administration of L-arginine on the stress response and its mechanism in neonatal chicks. Intracerebroventricular (i.c.v.) injection of L-arginine clearly attenuated the stress response in a dose-dependent manner, and induced sleep-like behavior during 10 min. To clarify the mechanism by which L-arginine induces sedative and hypnotic effects in chicks, we investigated the effects of nitric oxide (NO) synthase (NOS) inhibitors on L-arginine-induced sedative and hypnotic effects, and as well as the effects of a NO donor. L-Arginine-induced (1.9 micromol) sedative and hypnotic effects were attenuated by i.c.v. co-injection with a non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester HCl (400 nmol). In addition, the effects of L-arginine were slightly attenuated by the inactive isomer of the NOS inhibitor N(G)-nitro-D-arginine methyl ester HCl (400 nmol). The i.c.v. injection of 3-morpholinosylnomine hydrochloride, a spontaneous NO donor, had little effect on postures. The i.c.v. injection of L-arginine had no effect on NOx concentration at various brain sites. These results suggested that the contribution of NO generation via NOS may be low in the sedative and hypnotic actions of L-arginine. Therefore, L-arginine and/or its metabolites, excluding NO, may be necessary for these actions.

Intracerebroventricular (i.c.v.) injection of L-serine was shown to have sedative and hypnotic effects on neonatal chicks under acute stressful conditions. To clarify the central mechanism of these effects of L-serine, two experiments were done. First, we focused on the glycogenic pathway in which L-serine is converted into pyruvate and finally glucose. I.c.v. administration of pyruvate (0.84 micromol) did not induce any behavioral and endocrinological changes, while L-serine and glucose triggered sedative and hypnotic effects. Secondly, the relationship between the sedation by L-serine and the metabolism into other amino acids which have sedative effects was investigated in the telencephalon and diencephalon. In both brain areas, a dose-dependent increase was seen in L-serine, although other amino acids were not changed. In the present study, it was concluded that the sedative action of L-serine was not due to the action of its metabolite pyruvate, or to the action of other amino acids.

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of insomnia in oriental countries. This experiment was performed to investigate whether sanjoinine A, one of major alkaloid compounds of ZSS, has hypnotic effects and/or enhances pentobarbital-induced sleeping behaviors through the gamma-aminobutyric acid (GABA)-ergic systems. Sanjoinine A itself did not induce sleeping at the higher dose used in this experiment. However, sanjoinine A prolonged sleeping time and reduced the sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a GABA(A) receptor agonist. Sanjoinine A also increased sleeping rate and sleeping time when administered combined with pentobarbital at a sub-hypnotic dosage and showed synergistic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. In addition, both sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A also showed similar effects with muscimol in potentiating chloride influx inducing effects of low dose pentobarbital. Sanjoinine A decreased GABA(A) receptor alpha-subunit expression and increased gamma-subunit expression, and had no effects on the abundance of beta-subunits in primary cultured cerebellar granule cells, showing different subunit expression from pentobarbital. In addition, we found that sanjoinine A also enhanced expression of glutamic acid decarboxylase (GAD), but pentobarbital did not. In conclusion, sanjoinine A itself does not induce sleeping, but it augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems.

Background/aim: The aim of this study was to investigate the effects of conscious sedation with 40% nitrous oxide/oxygen (N2O/O2) on cognitive functions. Materials and methods: Forty dental patients referred to the sedation unit at Gazi University Faculty of Dentistry Department of Oral and Maxillofacial Surgery received a combination of 40% N2O/O2 inhalation for conscious sedation. Psychometric tests were applied three times: before sedation, during sedation, and at the end of the recovery, for assessing cognitive functions. Results: The results of this study showed that the 40% N2O/O2 combination impaired cognitive functions during the conscious sedation. Recovery of most of the cognitive functions occurred 15 min after sedation. However, in addition to the persistence of 'hypnotic effects' and 'sensations of isolation' during the recovery period, 'motor loss value' showed more cognitive impairment 15 min after sedation than before the sedation period, and, thus, the ability to execute fine motor skills was not totally recovered by then. Conclusion: The results of this study could be crucial for informing patients about avoiding attentive activities soon after conscious sedation via 40% N2O/O2.

Procedures for estimating hypnotic depth have been used for more than 70 years. This study predicted self-reported hypnotic depth from the phenomenological and behavioral variables of the Phenomenology of Consciousness Inventory-Hypnotic Assessment Procedure (PCI-HAP). Participants were divided into 2 groups; 1 was used to generate regression equations, and the other group was used for cross-validation. Both imagery vividness during hypnosis (imagoic suggestibility) and the PCI pHGS measure of hypnotic depth (hypnoidal state) accounted for most of the variance in self-reported hypnotic depth. The above results, further supported by correlational and 3-D visual analyses, are consistent with other researchers' observations that ratings of hypnotic depth are a function of: (a) alterations in subjective experience, and (b) the perception of responsiveness to suggestions. The findings are also congruent with J. Holroyd's hypothesis that suggestibility and altered-state effects interact to produce hypnotic effects.

Adolescents differ from adults in their sensitivity to a variety of psychoactive drugs. For example, adolescent rats are less sensitive to locomotor stimulant and stereotypic effects of amphetamine as well as to motor-impairing and hypnotic effects of ethanol while more sensitive to ethanol-induced disruption of brain plasticity.The current study further explored age differences in psychopharmacological sensitivity by examining the effects of d-amphetamine (1.0 and 4.0 mg/kg) or ethanol (0.5, 1.0 and 1.5 g/kg) given interperitoneally on the acoustic startle response (ASR) and prepulse inhibition (PPI) in male adolescent and adult Sprague-Dawley rats.The animals were given five startle trials (120 dB for 40 ms) before semi-randomized presentation of 12 startle trials interspersed with ten trials at each prepulse intensity (40 ms pulse of 5, 10, or 20 dB above background; 100 ms before the startle stimulus).Adolescent controls showed significantly less PPI than adults, replicating previous ontogenetic findings. The higher dose of amphetamine disrupted PPI in adult but not in adolescent animals, extending previous reports of an adolescent insensitivity to amphetamine to include this measure of sensorimotor gating. Ethanol exposure failed to alter PPI at either age, although both the 1.0 and 1.5 g/kg doses of ethanol significantly suppressed the magnitude of the ASR at both ages, potentially reflecting sedative or anxiolytic effects.These data provide further evidence of the relative insensitivity of adolescent animals to amphetamine, although no age effects were found in terms of ethanol sensitivity using these measures of startle and sensorimotor gating.

Besides having important hormonal effects, progesterone has depressant and hypnotic effects on the brain. In this study, we compared women in the follicular phase with low progesterone levels and in the luteal phase with high progesterone levels regarding their anesthetic requirements. Twenty patients with menstrual cycle days from 1 to 10 (follicular group) and 20 patients with menstrual cycle days from 18 to 24 (luteal group) were included in the study. Anesthesia was induced with fentanyl and thiopental; relaxation was secured with rocuronium, and anesthesia was maintained with a mixture of nitrous oxide 2 L/min and oxygen 2 L/min plus sevoflurane. The delivered sevoflurane concentration was adjusted to sustain a constant bispectral index value that averaged 46 in both groups. To determine the progesterone levels, blood samples were taken from all patients before surgery. We found that progesterone levels were 0.86 +/- 0.30 ng/mL in the follicular group and 7.48 +/- 3.86 ng/mL in the luteal group. The minimum alveolar anesthetic concentration (MAC)-hour (MAC-h) value of sevoflurane in the follicular group (1.55 +/- 0.18 MAC-h) was significantly larger than in the luteal group (1.3 +/- 0.13 MAC-h) (P0.0001). The sevoflurane requirements were larger in the follicular group during the maintenance phase of anesthesia. In conclusion, high progesterone levels during the luteal phase might be the cause of decreased anesthetic requirement.The aim of this study was to determine the effect of high progesterone levels on anesthetic requirement. We measured progesterone levels before surgery and calculated the sevoflurane dose (MAC-h) required to maintain a constant bispectral index value. The dose of sevoflurane correlated inversely with serum progesterone concentrations.

The present study examined the roles of NR2A and NR2B subunit-containing NMDA receptors in the mediation of the sedative/hypnotic effects of ethanol in mice. The ability of the competitive NMDA antagonist, CGP-37849 (0, 1, or 3 mg/kg), and the NR2B-selective antagonist, Ro 25-6981 (0, 3, or 10 mg/kg), to alter (3 g/kg) ethanol-induced sleep time was measured in C57BL/6J mice and NR2A knockout (KO) mice. The results show that pretreatment with either antagonist significantly potentiated the sedative/hypnotic effects of ethanol in C57BL/6J mice. These effects were not significantly altered in NR2A KO mice. Basal sleep time responses to ethanol were also normal in NR2A KO mice. These findings confirm a major role for NMDA receptors in the acute intoxicating actions of ethanol and provide tentative support for a prepotent role of the NR2B subunit in these effects.

The purpose of this study was to evaluate the sedative and hypnotic effects of Eucommiol, a monomer compound extracted from male Eucommia flowers using a system solvent method. Eucommiol shows significant effects in mice, including reduced spontaneous activity, and increased the sleep ratio or lengthened the sleep time with a subthreshold or superthreshold dose of pentobarbital sodium, respectively. In addition, could effectively shorten sleep latency, reduce convulsion rate and prolong convulsion latency. These findings intensely indicated that Eucommiol has excellent sedative and hypnotic effects.

This study aimed to explore new methodologies in insomnia research, namely whether actigraphy was suitable to show hypnotic effects over weeks in insomnia, and to compare an automated method of questionnaire data collection with traditional methods. Thirty-eight insomniacs took part in a 5-week, double-blind, placebo-controlled study of the effects of 2 weeks of administration of temazepam 20 mg on sleep. Outcome measures were actigraphy and daily St Mary's Hospital Sleep Questionnaires (SMHSQ). Actigraphy was performed using Actiwatch (CNT) and analysed using both the automated Actiwatch sleep analysis software and non-parametric analysis of rest-activity rhythms. The questionnaires were administered as straightforward pencil-and-paper for half of the time and an automated telephoned system for the other half. The experimental paradigm allowed within-subject comparison of traditional and automated data collection, both on and off drug. Actigraphy showed a high degree of inter-subject variability but, nevertheless, some sleep variables (Fragmentation Index, Actual Sleep Time %) showed significant improvement during drug treatment, and Sleep Efficiency and Actual Sleep Time were significantly worsened during the first post-drug week. Nonparametric circadian rhythm analysis showed no significant effect. Subjective data from the SMHSQ showed significant drug effects and there was no significant difference in scores between the automated and pencil-and-paper methods; automated data collection was slightly more acceptable to patients and minimized data entry and management. Effect sizes using within-subject and between-subject comparisons were calculated for the subjective and objective measures to inform future studies

UNLABELLED There is some controversy in the literature about whether auditory steady-state responses (ASSRs) can be reliably recorded in all subjects and whether these responses consistently decrease in amplitude during drowsiness. In 10 subjects, 40-Hz ASSRs became significantly different from background electroencephalogram activity with a probability of P < 0.01 and an average time of 22 s (range, 2-92 s), provided that the responses were analyzed with time-domain averaging rather than spectral averaging. In a second experiment with 10 subjects, 40-Hz ASSRs recorded between the vertex and posterior neck consistently decreased in amplitude during drowsiness and sleep. Findings that the ASSR may occasionally increase during drowsiness may be explained by postauricular muscle responses recorded from a mastoid reference. These may occur during drowsiness in association with rolling-eye movements. ASSRs recorded between the vertex and posterior neck are not distorted by these reflexes. These findings combine with previous literature on the effects of general anesthetics on the ASSR to confirm that the ASSR is a valid option for monitoring the hypnotic effects of general anesthetics. IMPLICATIONS Auditory steady-state responses to stimuli presented at rates near 40 Hz can be used to monitor anesthesia. These responses can be quickly and reliably recorded during both sleep and wakefulness, provided that appropriate averaging techniques are used.

We have demonstrated that large-dose IV melatonin can exert hypnotic effects similar to those caused by thiopental and propofol. In this study, we compared the electroencephalographic (EEG) effects of melatonin with those of thiopental and propofol. Sprague-Dawley rats were assigned to receive equipotent bolus doses of thiopental (23.8 mg/kg), propofol (14.9 mg/kg), or melatonin (312 mg/kg). EEG effects were recorded at periodic intervals over 10 minutes. Of eight processed EEG variables analyzed, only relative total power (rTP), relative spectral edge 95% (rSE95), and relative approximate entropy (rAE) were altered by all drugs compared with their control vehicles. Drug administration decreased the values relative to baseline, with subsequent return toward baseline during the 10-min time course. Thiopental significantly increased rTP, whereas propofol and melatonin did not. All drugs significantly decreased rSE95. However, the time course of peak effect and duration differed for each, with melatonin exhibiting a slower onset and a more sustained EEG effect. All drugs significantly decreased rAE, with similar time courses for thiopental and propofol and a slower onset/longer duration for melatonin. Melatonin produced effects on processed EEG variables similar to those of thiopental and propofol, specifically a decrease in the rSE95 and a decrease in the rAE.Anesthetic doses of melatonin produced effects on processed electroencephalographic variables similar to those of thiopental and propofol.

Disparate opinions about the importance of the assessment of hypnotizability reflect very different ideas about what hypnosis is, the relevance of hypnotizability to psychotherapy and treatment outcome, and the importance of gathering scientific data to document treatment effectiveness and the presence of hypnotic effects. In this article, we argue that in recent years important developments have occurred in the conceptualization, assessment, and technical aspects of hypnotic intervention that imply that clinicians who eschew the use of hypnotizability assessment ought to reconsider their position. In making this argument, we will discuss reasons for assessing hypnotizability, the relation between hypnotizability and treatment outcome, and practical considerations in the assessment of hypnotizability.

Benzodiazepines, one of a group of structurally-related drugs with sedative and hypnotic effects, were originally developed as an alternative to barbiturates. During the 1970s they became one of the most prescribed drugs in general practices, and valium and dalmane were among the most-frequently advertised products in leading medical journals. Research into benzodiazepine prescription in general practice has shown that many are repeat prescriptions, with minimal contact between doctor and patient. Prevalence of benzodiazepine use was found to be higher in women, the elderly, the chronically ill and those with family, social and economic problems. Despite the establishment of guidelines discouraging long-term benzodiazepine prescribing, it remains a significant feature in medical practice in the UK. The guidelines may not have sufficiently considered the negative therapeutic implications for legitimate patients of restricting availability. A plan for effective benzodiazepine regulation requires a grasp of the dynamics of drug prescribing, consumption and diversion. The effects of harmful drug use in socially disadvantaged areas underlines the urgent need for further quantitative and qualitative research in this area.

The bispectral index (BIS) has been developed in adults and correlates well with clinical hypnotic effects of anesthetics. We investigated whether BIS reflects clinical markers of hypnosis and demonstrates agent dose-responsiveness in infants and children. In an observational arm of this study, BIS values in children undergoing general anesthesia were observed and compared with similar data collected previously in a study of adults. In a second arm of the study, a range of steady-state end-tidal concentrations of sevoflurane was administered and corresponding BIS documented. Data were examined for differences between infants (0-2 yr) and children (2-12 yr). No difference was seen in BIS values in children before induction, during maintenance, and on emergence compared with adult values. There was no difference in BIS between infants and children at similar clinical levels of anesthesia. In children and infants, BIS was inversely proportional to the end-tidal concentration of sevoflurane. The sevoflurane concentration for a BIS = 50 (95% confidence interval) was significantly different: 1. 55% (1.40-1.70) for infants versus 1.25% (1.12-1.37) for children. Although validation with specific behavioral end points was not possible, BIS correlated with clinical indicators of anesthesia in children as it did in adults: as depth of anesthesia increased, BIS diminished. BIS correlated with sevoflurane concentration in infants and children. The concentration-response difference between infants and children was consistent with data showing that minimum alveolar concentration is higher in children less than 1 yr of age.The use of bispectral index (BIS) during general anesthesia improves the titration of anesthetics in adults. The data from this study suggest that the same equipment and method of electroencephalogram analysis may be applied to infants and children.