Injection Of Diazepam Research Articles

Effect of intramuscular diazepam infusion on herpes zoster-related pain in older patients: a randomized, double-blind, placebo-controlled trial

ObjectivesThis study evaluated the effectiveness, psychological effects, and sleep quality using intramuscular diazepam infusion compared with placebo in patients with herpes zoster (HZ)-related pain.MethodsThe patients were randomized to either the diazepam or control group. The diazepam group received an intramuscular injection of diazepam for 3 consecutive days, while the control group received an intramuscular injection of 0.9% normal saline. The primary outcome was pain relief on posttreatment day 4, as measured using the Visual Analog Scale (VAS). Moreover, anxiety and depression were evaluated using the Generalized Anxiety Disorder-7 (GAD7) and Patient Health Questionnaire-9 (PHQ9), respectively. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI).ResultsIn total, 78 patients were enrolled in the trial. The mean differences in VAS scores between the two groups were 0.62 (P = 0.049) on posttreatment day 3 and 0.66 (P = 0.037) on posttreatment day 4. The effective rates of pain management in the diazepam group ranged from 10.26 to 66.67%, which were higher than those in the control group on posttreatment days 3 and 4 (P < 0.05). The mean difference in PSQI scores between the diazepam and control groups was 1.36 (P = 0.034) on posttreatment day 7. No differences were found in the incidence of analgesia-adverse 1reactions between the diazepam and placebo groups.ConclusionsThe intramuscular injection of diazepam for 3 consecutive days provides effective pain management and improves the quality of life. Our study suggests that diazepam is more effective than the placebo in patients with HZ-related pain.Trial registrationThe study was prospectively registered at https://www.isrctn.com/trialist(Registration date: 24/01/2018; Trial ID: ISRCTN12682696).

Possible involvement of GABAergic system on central amygdala Mediated anxiolytic effect of agmatine in rats

Objectives To study the pharmacological interactions between agmatine and gamma aminobutyric acid (GABA) modulatory agents in the regulation of anxiety-like behavior in rats. Materials and methods Male Wistar rats were treated drugs per se or in combination and 15 min after last injection were subjected to elevated plus-maze (EPM) test. Anxiety-like behavior was evaluated by measuring behavioral conventional readout, open arm activity (duration and/or entries) for 5-minute duration. Results Acute intra-central amygdala (CeA) injection of agmatine (0.1-0.6 μmol/site/rat), muscimol (0.25-1 nmol/site/rat), diazepam (5-20 μg/site/rat) and allopregnanolone (2-8 μg/site/rat) increased open arm entries of the rats in EPM suggesting anxiolytic effect in dose dependent manner. Moreover, the anxiolytic effect at subeffective dose of agmatine (0.1 μmol/site/rat) was potentiated by subeffective dose of muscimol (0.25 nmol/site/rat), diazepam (5 μg/site/rat) and allopregnanolone (4 μg/site/rat). Whereas, pretreatment with GABAA receptor antagonist, bicuculline (10 ng/site/rat) blocked the anxiolytic effect of agmatine and its synergistic effect of agmatine plus muscimol. Similarly, benzodiazepine (BZD) receptor antagonist, flumazenil (15 μg/site/rat) and GABA allosteric modulator antagonist, RO 15-45 13 (10 μg/site/rat) reduced the anxiolytic effect of agmatine, given alone and with diazepam and allopregnanolone, respectively. Conclusion These results indicated that anxiolytic effect of agmatine is medicated via GABAergic mechanisms, probably conciliated by the GABAA receptor subtypes. Modulation of interplay between agmatine and GABAA receptor activity might be a pertinent solution for the regulation of anxiety.

Behavioral and electrophysiological (ECoG) effects of haplophyllum robustum and TRPA1 antagonist in adult male wistar rats

This article aimed to investigate the effects of Haplophyllum robustum hydroalcoholic extract on animals’ behavioral and electrocorticographic changes. This plant is mainly found in Turkey, Iran, and Central Asia, and is reported to have convulsive effects.In this article, we worked on the effects of its hydroalcoholic extract on electrocorticography (ECoG), along with changes induced by intracerebroventricular administration of GABAA antagonists. Furthermore, the effects of low doses of this extract on behavioral depression were examined.Four animal sets were used to compare ECoG in Wistar rats. A group of negative control, a group of positive control (PTZ), and two groups received an injection of plant extract (500 mg/kg, ip), with or without administration of Diazepam (5 mg/kg).Also, three sets were applied to compare receiving and not receiving intracerebroventricular (icv) injection of Transient receptor potential ankyrin 1 antagonist (HC-030031) (2 μg/kg) on plant-induced seizure delay and animal death. Two groups of control and a group with plant extract together with TRPA1 antagonist were administrated.Furthermore, in the present study, the forced swimming test (FST) was used as a model of depression. The behaviors of animals in three groups of negative control and positive control (Fluoxetine) and plant extract (200 mg/kg, ip) were compared.According to the ECoG, high doses of extract of plants led to seizures similar to PTZ, which were then reduced by diazepam injection. At this dose, injection of TRPA1 antagonist did not significantly delay the onset of seizures or the death of the animals. Further, a subconvulsive dose of hydroalcoholic plant extracts was equally effective in treating depression as Fluoxetine injections.

Analysis of injectable drugs (Pentazocine and Diazepam) sampled from shops and companies in Anambra State, Nigeria

The incidences of drug adulteration and drug resistance have been a major problem facing mankind in recent years. Low and medium-income countries like Nigeria are most affected. An investigation was carried out to determine the quality of Pentazocine and Diazepam injections in circulation in Anambra State. The injections were sampled from different markets, shops, and pharmaceutical companies within the State. Imported and locally manufactured brands of the injections were analysed. Identification, pH, Assays, Bacteria Endotoxin, sterility, and sub-visible particulate matter contamination were analysed. The results of the Identification, Bacteria Endotoxin (BET), Particulate matter count, and pH are all within the British Pharmacopeia. The Pentazocine Assays obtained were (98.31%- 102.5%) which are within the British Pharmacopeia limit of (95% – 105%). This is good for health management. The Assays of two of the Diazepam injections tested were between (111.33% - 111.53%), which is above the approved British Pharmacopeia limit of (90%-110%). This is an indication of high level of impurities and not good for health care management.

Altered GABAA receptor function in women with endometriosis: a possible pain-related mechanism.

The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABAA ) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women. 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18-40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection. Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels. Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist.

Protective effect of methanolic extract of Areca catechu nut on ethanol withdrawal symptoms in mice

BackgroundThe purpose of the current study was to examine the potential impact of a methanolic extract of Areca catechu nut (MAN) on handling-induced convulsions (HIC), anxiety and anhedonia behaviour of alcohol-withdrawn mice. 30 female Swiss albino mice were divided into 5 groups, each with 6 animals. Group 1 (saline withdrawal) received saline during the 3-day alcohol/saline induction phase, while the other 4 groups (alcohol withdrawal) received 20% v/v ethanol (1.25 ml/100 g body weight, i.p.; 20% v/v ethanol was made from absolute ethanol with 79.9 ml saline + 0.1 ml fomepizole, an alcohol dehydrogenase inhibitor). Day four (test day) involved studying handling-induced convulsions; open field test (OFT), elevated plus maze test (EPM), marble burying test (MBT) for anxiety; 24-h sucrose preference test (SPT) for anhedonia in mice. On the test day, Group I and II (saline withdrawal and alcohol withdrawal) received oral treatments with 1% w/v sodium carboxyl methylcellulose 1 h prior to the behavioural testing. Group III received an injection of diazepam (1 mg/kg, i.p., 30 min prior) and Group IV and V were treated with two different doses of MAN (50 and 100 mg/kg, p.o.) 1 h prior to the behavioural test.ResultsAt doses of 50 and 100 mg/kg, p.o., the Areca catechu nut methanolic extract significantly reduced handling convulsions and anxiety, and had an anti-anhedonic effect using various evaluation criteria, such as convulsion score (HIC), no. of central and peripheral line crossings (OFT), % entries and time spent in open arms (EPM), no. of marbles buried (MBT), and sucrose intake ratio (SPT) in alcohol-withdrawn mice.ConclusionIn mice undergoing alcohol withdrawal, Areca catechu nut extract (MAN) greatly lessens handling-induced convulsions, anxiety and depression symptoms.Graphical

Synergistic effects of applying static magnetic fields and diazepam to improve EEG abnormalities in the pilocarpine epilepsy rat model

The lithium-pilocarpine rat model is a well-known model of temporal epilepsy. Recently we found that transcranial static magnetic stimulation (tSMS) delay and reduce the signs of EEG in this model. We aim to test the effect of combining the therapeutic action of tSMS and diazepam, a drug used to treat status epilepticus. We induce epilepsy in 12 Sprague–Dawley rats. Animals were classified as “magnet” when a magnetic neodymium cylinder was placed over the skull or “control” when a stainless-steel replica was used. Diazepam was injected 60-min after the second doses of pilocarpine injection. We found a reduction in the number of spikes/minute for magnet condition compared with sham condition, reaching significance at 60 min after diazepam injection. The Root-Mean-Square shown a significant reduction in magnet animals compared with those receiving diazepam (Tukey’s-test 30 and 60 min after diazepam injection, p < 0.01; 40 and 50 min after diazepam injection, p < 0.05). Furthermore, the power spectrum analysis shown a reduction in delta, theta, alpha and beta bands, on the diazepam + magnet animals compared to the diazepam + sham group. Analysis of high-frequency oscillations revealed an increased in the ripples due to pilocarpine being reduced by diazepam. Our results demonstrate that application of tSMS previously to diazepam potentiates the effect of the drug by reducing the electroencephalographic pattern associated with epileptiform discharges. We suggest a new synergistic cooperation between pharmacology and neuromodulation as a future treatment for epilepsy.

Pharmaceutical Quality Assurance of Diazepam Injection at the National Health Laboratory of Mali

Objectives: In a world marked by the increase in chemoresistance leading to the adoption of therapeutic combinations, the advent of generic multi-source drugs, the spread of counterfeiting and substandard drugs, often without active ingredients or falsified active ingredients, a Greater vigilance by pharmaceutical regulatory authorities is needed. Drug Post-Marketing Surveillance (PMS) therefore plays an important role in detecting poor quality products on the market. Methods: The survey covered certain regions and certain points of sale. It aimed to assess the quality of Diazepam injection available on the market. The selection of drugs and geographic areas was made using risk-based sampling using the Drug Risk Assessment Tool (MedRS) developed by USP / PQM +. Results: A total of 44 samples were analyzed according to a risk-based protocol, of which 32 were compliant with a rate of 91% against 12 non-compliant or 9% (P≤0,05). Non-compliant drugs were mainly from the public sector. We also found that all samples were unregistered. Conclusion: The results clearly raise the issue of registration of drugs before their market authorization and the importance of continuous quality control and post-marketing drug analysis to ensure health and guarantee access to quality medicines for the health and well-being of populations.

Pharmaceutical Quality Assurance of Diazepam Injection at the National Health Laboratory of Mali

Pharmaceutical Quality Assurance of Diazepam Injection at the National Health Laboratory of Mali

Mucuna pruriens seed protects the hippocampal neurons and abrogates seizure indices in chemically-convulsed mice: Evidence of the Nrf2 expression defense pathway

The anti-convulsant mechanisms and neuroprotective effects of Mucuna pruriens (MP) seed in male BALB/c mice were evaluated. Ninety mice were kindled with picrotoxin, strychnine, or pilocarpine hydrochloride at the 30th minute of intraperitoneal injection (i.p) of normal saline (0.2 ml), MP (200, 100, 50 mg/kg), diazepam (7.5 mg/kg), or haloperidol (5 mg/kg). The onset of convulsion and percentage mortality was recorded. The histoarchitectural and immunohistochemical profiles of the brains were determined. Data were expressed as mean ± SEM with a one-way analysis of variance (ANOVA), while p < 0.05 was considered significant. There was a significant prolongation of the latency to first seizure across the treatment groups following picrotoxin, and pilocarpine-induced convulsion; a decrease in percentage mortality in the MP (50 mg/kg) treatment group, and an increase in the hippocampal nuclear factor erythroid 2-related factor 2 count, and Neu-N expression in the MP (200 mg/kg, and 100 mg/kg) treated mice. Treatment with MP seed may abolish seizure occurrence and consequential mortality; mechanisms traceable to its GABAergic expression and hippocampal NRF 2 and Neu N expression.

Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice.

Our study aims at comparing in C57/Bl male mice, the impact of repeated injections of baclofen (an agonist of GABAB receptor) or diazepam (a benzodiazepine acting through a positive allosteric modulation of GABAA receptor) administered during the alcohol-withdrawal period on hippocampus-dependent memory impairments and brain regional glucocorticoid dysfunction after a short (1-week) or a long (4-week) abstinence. Hence, mice were submitted to a 6-month alcohol consumption (12%v/v) and were progressively withdrawn to water. Then, after a 1- or 4-weeks abstinence, they were submitted to a contextual memory task followed by measurements of corticosterone concentrations in the dorsal hippocampus (dHPC), the ventral hippocampus (vHPC) and the prefrontal cortex (PFC). Results showed that 1- and 4-week withdrawn mice exhibited a severe memory deficit and a significant abnormal rise of the test-induced increase of corticosterone (TICC) in the dHPC, as compared to water-controls or to mice still under alcohol consumption. Repeated daily systemic administrations of decreasing doses of diazepam (ranged from 0.5 to 0.12 mg/kg) or baclofen (ranged from 1.5 to 0.37 mg/kg) during the last 15 days of the withdrawal period, normalized both memory and TICC scores in the dHPC in 1-week withdrawn animals; in contrast, only baclofen-withdrawn mice showed both normal memory performance and TICC scores in the dHPC after a 4-week withdrawal period. In conclusion, the memory improvement observed in 4-week withdrawn mice administered with baclofen stem from the protracted normalization of glucocorticoid activity in the dHPC, a phenomenon encountered only transitorily in diazepam-treated withdrawn mice.

A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy

Status epilepticus (SE) is a medical emergency associated with acute severe systemic damage and high mortality. Moreover, symptomatic SE is one of the highest risk factors for epileptogenesis. While the antiepileptic drugs (AEDs) are chosen in favor of acute control of SE, the potential short-term and long-term effects of such AEDs have been ignored in clinics. In this study, we hypothesized that AEDs that are used to control acute SE might affect the feasibility for the chronic development of epileptogenesis after SE. Therefore, we sought to compare the epileptogenic effects of SE that are terminated by three AEDs, i.e., diazepam, midazolam, and pentobarbital, which are widely used as first-line anti-SE AEDs. For this purpose, we used a mouse model of SE induced by intraperitoneal (i.p.) injection of lithium chloride (LiCl)-pilocarpine. The pilocarpine-induced SE was terminated with diazepam, midazolam, or pentobarbital. Then we compared short-term and long-term effects of SE with different AED treatments by examining SE-associated mortality and behavioral spontaneous recurrent seizures (SRSs) and by using magnetic resonance imaging (MRI) and immunohistochemistry to evaluate pathological and cellular alterations of mice in the different treatment groups. We found that i.p. injections of diazepam (5 mg/kg), midazolam (10 mg/kg), and pentobarbital (37.5 mg/kg) were able to terminate acute pilocarpine-SE effectively, while pentobarbital treatment showed less neuroprotective action against lethality in the short phase following SE. Long-term evaluation following SE revealed that SE treated with midazolam had resulted in relatively less behavioral SRS, less hippocampal atrophy, and milder neuronal loss and gliosis. Our data revealed an obvious advantage of midazolam vs. diazepam or pentobarbital in protecting the brain from epileptogenesis. Therefore, if midazolam provides as strong action to quench SE as other AEDs in clinics, midazolam should be the first choice of anti-SE AEDs as it provides additional benefits against epileptogenesis.

Effects of CYP2C19*17 genetic polymorphisms on plasma and saliva concentrations of diazepam in patients with alcohol withdrawal syndrome.

Diazepam is one of the most commonly prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions. Previous studies have shown that the metabolism of diazepam involves the CYP2C19 isoenzyme, whose activity is highly dependent on polymorphism of the encoding gene. The study aimed to investigate the effects of CYP2C19*17 genetic polymorphisms on plasma and saliva concentrations of diazepam as well as its impact on the efficacy and safety rates of therapy in patients with AWS. The study was conducted on 100 Russian male patients suffering from the AWS who received diazepam injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time PCR with allele-specific hybridization. The efficacy and safety assessment was performed using psychometric scales. Based on the results of the study, we revealed differences in the efficacy and safety of therapy in patients with different CYP2C19 -806C>T genotypes. Therapeutic drug monitoring revealed the statistically significant difference in the levels of diazepam plasma concentration: (CC) 251.76 (214.43; 310.61) vs. (CT+TT) 89.74 (54.18; 179.13); P = 0.003, and diazepam saliva concentration: (CC) 3.86 (3.22; 5.12) vs. (CT+TT) 0.79 (0.44; 1.56); P = 0.003. Our study showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant differences in plasma and saliva concentration levels of diazepam in patients carrying different genotypes.

LncRNA GAS5 promotes epilepsy progression through the epigenetic repression of miR-219, in turn affecting CaMKIIγ/NMDAR pathway

It has been widely reported that dysregulated long-chain noncoding RNAs (lncRNAs) are closely associated with epilepsy. This study aimed to probe the function of lncRNA growth arrest-specific 5 (GAS5), microRNA (miR)-219 and Calmodulin-dependent protein kinase II (CaMKII)γ/N-methyl-D-aspartate receptor (NMDAR) pathway in epilepsy. Epileptic cell and animal models were constructed using magnesium deficiency treatment and diazepam injection, respectively. GAS5 and miR-219 expressions in epileptic cell and animal models were determined using qRT-PCR assay. The protein levels of CaMKIIγ, NMDAR and apoptosis-related proteins levels were assessed by western blot. Cell counting kit-8 (CCK-8) assay was employed to determine cell proliferation. Besides, TNFα, IL-1β, IL-6 and IL-8 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Furthermore, cell apoptosis was evaluated using TUNEL staining and flow cytometric analysis. Finally, the binding relationship between GAS5 and EZH2 was verified using RIP and ChIP assay. Our results revealed that GAS5 was markedly upregulated in epileptic cell and animal models, while miR-219 was down-regulated. GAS5 knockdown dramatically increased cell proliferation of epileptic cells, whereas suppressed inflammation and the apoptosis. Furthermore, our results showed that GAS5 epigenetically suppressed transcriptional miR-219 expression via binding to EZH2. miR-219 mimics significantly enhanced cell proliferation of epileptic cells, while inhibited inflammation and the apoptosis, which was neutralized by CaMKIIγ overexpression. Finally, miR-219 inhibition reversed the effects of GAS5 silence on epileptic cells, which was eliminated by CaMKIIγ inhibition. In conclusion, GAS5 affected inflammatory response and cell apoptosis of epilepsy via inhibiting miR-219 and further regulating CaMKIIγ/NMDAR pathway (See graphic summary in Supplementary Material).

Comparing intensity of pain due to intravenous injection of sodium thiopental, propofol, diazepam, and etomidate during induction of general anesthesia.

The aim of the present study was to compare the pain intensity due to intravenous injection of sodium thiopental, propofol, diazepam, and etomidate during the induction of general anesthesia. This was a non-controlled quasi-experimental double-blinded study performed on eligible patients referred to the operating room of Shahid Beheshti Hospital in Yasouj. A total of 200 patients were randomly selected by convenience sampling and based on a table of random numbers generated on a computer. They were then randomly divided into four intervention groups based on random blocks (sodium thiopental, propofol, etomidate, and diazepam). Finally, the collected data were analyzed using descriptive as well as analytical statistical tests such as Chi-square, analysis of covariance (ANCOVA), and Bonferroni post hoc test were analyzed in SPSS ver. 24. The results of the present study showed that the diazepam group experienced the highest pain intensity (8.42) compared to other groups, which was statistically significant (P = 0.001). Also, the sodium thiopental group experienced the highest pain (6.92) after the diazepam group, which was also statistically significant as compared to the other remaining two groups (P = 0.001). Propofol and etomidate groups experienced the lowest pain intensity (3.30 and 3.26, respectively). The present study revealed that the use of diazepam and sodium thiopental as anesthetic drugs was generally associated with greater pain intensity during injection and less hemodynamic stability. The results of the present study indicated that propofol and etomidate are preferred over diazepam and sodium thiopental in abdominal and gastrointestinal surgeries, considering their less pain intensity and fewer hemodynamic changes.

Diazepam attenuates the effects of cocaine on locomotion, 50-kHz ultrasonic vocalizations and phasic dopamine in the nucleus accumbens of rats.

Currently, there is no effective drug to treat cocaine-use disorder, which affects millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine concentrations in the nucleus accumbens of rodents and block the increase in dopamine levels and appetitive 50-kHz ultrasonic vocalizations (USVs) induced by amphetamine in rats. Here, we tested whether administration of 2.5-mg·kg-1 diazepam (i.p.) in adult male rats could block the effects of 20-mg·kg-1 cocaine (i.p.) on electrically evoked phasic dopamine signals in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity. Cocaine injection increased evoked dopamine signals up to threefold within 5 min, and the increase was significantly higher than baseline for at least 75 min. The injection of diazepam, 5 min after cocaine, attenuated the cocaine effect by nearly 50%, and this attenuation was maintained for at least 40 min. Behaviourally, cocaine increased the number of appetitive 50-kHz calls by about 12-fold. Diazepam significantly blocked this effect for the entire duration of the session. Also, cocaine-treated rats were more active than controls and diazepam significantly attenuated cocaine-induced locomotion, by up to 50%. These results suggest that the neurochemical and psychostimulant effects of cocaine can be mitigated by diazepam. This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.

A case of thyroid storm caused by Graves\u2019 disease misdiagnosed as panic attack due to panic disorder

BackgroundGraves’ disease is characterized by hyperthyroidism and its symptoms often overlap with those of panic disorder, which may make it difficult to distinguish between the two conditions. In this report, we describe how proper diagnosis of thyroid disease in patients with mental illness can lead to appropriate treatment.Case presentationWe encountered a 34-year-old woman in whom thyroid crisis from Graves’ disease was misdiagnosed as panic attack. The patient was being managed as a case of panic disorder and bipolar disorder in a psychiatric outpatient setting. About 6 months before presentation she had lost about 16 kg in weight, and a month before presentation she developed several unpleasant symptoms as her condition worsened. Several weeks before she had had severe palpitations, tachycardia, and discomfort in her throat. She became unable to eat solids, ate only yogurt and gelatin, and felt it difficult to take psychiatric drugs.She visited our emergency outpatient department on a Sunday morning, presenting with nausea, severe tachycardia, fever, and restlessness with anxiety. We treated her as panic disorder with fever, but noted proptosis and considered the possibility of Graves’ disease. Thyroid function tests were performed even though data from her clinic was not available because it was a weekend.Because there was no improvement in her condition after her first visit, she returned to our hospital early the next morning. We had misdiagnosed her as having severe panic attacks due to panic disorder, and after a diazepam injection had allowed her to go home.Later that day, the thyroid function test results became available, and her symptoms and the results strongly indicated a thyroid storm. The endocrinology department was consulted immediately, and she was referred for hospitalization the next day. During hospitalization, she was treated with steroid and radioactive iodine therapy and was discharged from hospital in 3 weeks.ConclusionPsychiatrists and doctors engaged in psychosomatic medicine need to consider the possibility of severe hyperthyroidism as a differential diagnosis of panic disorder.

Characterization of pharmaco-EEG fingerprint and sleep-wake profiles of Lavandula angustifolia Mill. essential oil inhalation and diazepam administration in rats

Ethnopharmacological relevanceLavandula angustifolia Mill. Essential oil (Lavender EO) has a long history of medicinal use and is particularly claimed to possess anxiolytic and sedative properties. Lavender EO aromatherapy has been used to reduce distress and improve insomnia naturally. Increasing evidence appeared to show similarities between the effects of lavender EO and the anxiolytic drugs, benzodiazepines. However, its effects on sleep-wake and electrical brain patterns in comparison to that of the standard anxiolytic, diazepam, remained to be explored. Aim of the studyThe aim of this work was to investigate electroencephalography (EEG) profiles and sleep-pattern elicited by lavender EO inhalation compared to that of diazepam, a standard anxiolytic drug in in vivo rat model. Materials and methodsAdult male Wistar rats were anesthetized for electrode implantation on the frontal and parietal skulls. EEG signals were recorded for 180 min following intraperitoneal injection of diazepam (10 mg/kg) or during continuous inhalation of lavender EO (200 μL) or distilled water (control). Fast Fourier transform was used for the analyses of EEG power spectra and sleep-wake parameters. ResultsDuring a 30–60 min period, diazepam and lavender EO significantly increased frontal powers of 0.78–45.31 and 7.03–18.36 Hz, respectively. Both treatments also increased parietal powers with lower magnitudes of significant change. Significant increases in some frequency ranges remained until a 60–90 min period. Sleep-wake analyses also revealed that diazepam significantly reduced time spent in wake, increased time spent in non-rapid eye movement (NREM), increased episode duration of NREM, decreased numbers of wake episode and decreased rapid eye movement (REM) sleep latency. On the other hand, lavender EO only significantly decreased wake episodes and latency to REM sleep. Lavender EO inhalation reduced numbers of wake episode but maintain normal time spent in wake, NREM and REM sleeps. ConclusionsThese findings might suggest beneficial and distinct anxiolytic-like effects of lavender EO for sleep enhancing purposes.

Diazepam effects on local cortical neural activity during sleep in mice

GABA-ergic neurotransmission plays a key role in sleep regulatory mechanisms and in brain oscillations during sleep. Benzodiazepines such as diazepam are known to induce sedation and promote sleep, however, EEG spectral power in slow frequencies is typically reduced after the administration of benzodiazepines or similar compounds. EEG slow waves arise from a synchronous alternation between periods of cortical network activity (ON) and silence (OFF), and represent a sensitive marker of preceding sleep-wake history. Yet it remains unclear how benzodiazepines act on cortical neural activity during sleep. To address this, we obtained chronic recordings of local field potentials and multiunit activity (MUA) from deep cortical layers of the primary motor cortex in freely behaving mice after diazepam injection. We found that the amplitude of individual LFP slow waves was significantly reduced after diazepam injection and was accompanied by a lower incidence and duration of the corresponding neuronal OFF periods. Further investigation suggested that this is due to a disruption in the synchronisation of cortical neurons. Our data suggest that the state of global sleep and local cortical synchrony can be dissociated, and that the brain state induced by benzodiazepines is qualitatively different from spontaneous physiological sleep.

Assessing the Effect of Diazepam on Methamphetamine-Induced Seeking Behavior in Rats

Background: Relapse is a common problem in substance-use disorders. Accumulating evidence has shown that diazepam can reduce the abuse potential of some drugs. Objectives: We investigated the effects of diazepam during and after the withdrawal period on the reinstatement of conditioned place preference (CPP) induced by a single dose of methamphetamine in male Wistar rats. Methods: Three groups of rats were trained to acquire methamphetamine CPP. The rats in the control group received, respectively, saline and methamphetamine (1 mg/kg, daily, ip) in the extinction and priming phases. Two other groups (one and two) had a similar process, but the rats in group one received diazepam (3 mg/kg, daily, ip) in the extinction phase and those in group 2 received a single dose of diazepam just before the priming phase. The CPP was checked daily during all processes. Results: We showed that a 3-day period injection of methamphetamine (1 mg/kg) resulted in a positive conditioning score on the first day after conditioning. Also, 3 mg/kg of diazepam daily in the extinction period shortened the withdrawal period for one day and extinction happened on the 9th and 10th days. Diazepam also reduced the conditioning score at the reinstatement phase (P &lt; 0.01). Furthermore, diazepam injection (3 mg/kg) before the methamphetamine priming dose did not have any significant effect on the reinstatement of drug-seeking. Conclusions: This study demonstrated that administration of diazepam during the extinction period was associated with reduced maintenance and reinstatement of methamphetamine-induced CPP, while the single dose of diazepam could not prevent the reinstatement of methamphetamine.