Effect of Ocimum sanctum leaf extract in animal models of anxiety

Background: Anxiety is one of the most prominent psychiatry disorders related to common stress. Approximately two-thirds of anxious patients respond to currently available treatments but the magnitude of problem is still disappointing. Ocimum sanctum (OS), a perennial shrub grown in India, has anti-stress activity. Yet, there is a paucity of data regarding this. Aims and Objectives: This study aims to evaluate the anti-anxiolytic effect of OS leaf extract (OSLE) in Swiss albino mice. Materials and Methods: Elevated plus maze (EPM) and open field test are standardized tests done for screening anxiolytic effects of drugs. The animals were grouped and the tests were conducted and the results were compared with the standard drug diazepam. Results: There was significant increase in the time spent in open arm and number of open arm entries in the diazepam group and group receiving OSLE at dose of 100 mg/kg and 200 mg/kg in EPM test. Furthermore, in the open field test, there was significant increase in the number of square crossed and rearing in the diazepam group and OSLE at dose of 100 mg/kg and 200 mg/kg. Conclusion: OSLE shows significant anxiolytic effect in EPM and open field test models in Swiss albino mice. This can be further studied to open up new possibilities for new drug development for anxiety.

A preliminary study of antianxiety effect of Cuminum cyminum and comparison with standard drug

Background: Cuminum cyminum has been one of the commonly used home-based spices in India. It shows various properties such as antispasmodic, astringent, antiseptic, antioxidant, antimicrobial, analgesic, anti-inflammatory, antianxiety, anticonvulsant, and carminative. Aim and Objective: This study aimed to evaluate the antianxiety property of C. cyminum and its comparison with diazepam on albino rats. Materials and Methods: This study was conducted in Department of Pharmacology at a tertiary care center of Western Rajasthan. Adult albino rats of either sex (100–150 g) were divided into three groups. One group received distilled water and other two group received drugs – C. cyminum and Diazepam, respectively. Results: Antianxiety effect of C. cyminum was not significant in lower and medium doses (300 and 750 mg/kg). Significant antianxiety effect of C. cyminum was seen in higher dose (1000 mg/kg). Conclusion: On the basis of this study, it can be assumed that aqueous extract of C. cyminum could be a potential source to evaluate for the central nervous system disorders. Further studies are needed to explain the actual mechanism of action of C. cyminum at the cellular and molecular levels in detail.

Risperidone combined with diazepam for the treatment of alcohol-induced mental and behavioral disorders / 中国基层医药

Objective:To investigate the clinical efficacy of risperidone combined with diazepam in the treatment of alcohol-induced mental and behavioral disorders.Methods:Sixty patients with alcohol-induced mental and behavioral disorders admitted to Huainan Psychiatric Hospital from January 2018 to January 2022 were included in this study. They were randomly assigned to undergo either diazepam alone (control group, n = 30) or risperidone combined with diazepam (study group, n = 30). Clinical efficacy, Positive and Negative Syndrome Scale (PANSS) score, incidence of adverse reactions, quality of life, treatment satisfaction were compared between the two groups. Results:Total response rate differed significantly between the two groups ( Z = 6.25, P < 0.05). In the control group, PANSS scores measured before and after treatment were as follows: positive symptoms: (26.07 ± 3.70) points vs. (16.38 ± 2.04) points; negative symptoms: (24.04 ± 2.98) points vs. (13.86 ± 1.84) points; psychopathological symptoms: (44.06 ± 5.28) points vs. (31.83 ± 4.04) points; general score: (91.84 ± 9.76) points vs. (40.84 ± 6.26) points. In the study group, PANSS scores measured before and after treatment were as follows: positive symptoms: (25.84 ± 3.82) points vs. (10.30 ± 1.17) points; negative symptoms: (24.48 ± 3.26) points vs. (7.48 ± 0.82) points; psychopathological symptoms: (43.28 ± 5.21) points vs. (21.06 ± 3.72) points; general score: (92.06 ± 9.85) points vs. (68.27 ± 7.02) points. There were no significant differences in above indices measured before treatment between the two groups (all P > 0.05). After treatment, scores of positive, negative, psychopathological symptoms and general scores in the study group were significantly lower than those in the control group ( t = 14.16, 17.34, 10.74, 15.97, all P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Before and after treatment, the quality of life scores (physiological, psychological, social and environmental scores) of the control group were (12.64 ± 2.50) points vs. (13.87 ± 2.16) points; (12.47 ± 2.12) points vs. (13.28 ± 2.18) points; (9.54 ± 2.16) points vs. (14.20 ± 1.27) points; (10.97 ± 1.84) points vs. (12.78 ± 2.42) points. Before and after treatment, the quality of life scores (physiological, psychological, social and environmental scores) of the study group were (12.68 ± 2.53) points vs. (15.37 ± 2.07) points; (12.49 ± 2.14) points vs. (14.90 ± 2.20) points; (9.37 ± 2.14) points vs. (15.03 ± 1.27) points; (10.94 ± 1.81) points vs. (13.86 ± 2.18) points. After treatment, physiological, psychological, social and environmental scores in the study group were significantly higher than those in the control group ( t = 2.74, 2.86, 2.50, 2.81, all P < 0.001). There was significant difference in treatment satisfaction between the two groups ( χ2 =5.19, P = 0.022). Conclusion:Risperidone combined with diazepam can help improve the clinical symptoms of patients with alcohol-caused mental and behavioral disorders, further improves the treatment effect and quality of life, and is safe.

Uso inapropiado de psicofármacos prescritos: diazepam intravenoso en la emergencia psiquiátrica / Inappropriate use of prescribed psychotropic drugs: Intravenous diazepam in the psychiatric emergency

RESUMEN Las benzodiacepinas (BZD) son medicamentos esenciales en el tratamiento de diferentes problemas de salud: en el Petitorio Nacional de Medicamentos de nuestro país figuran cinco de ellas autorizadas para administración oral o parenteral. Al inicio de su uso en la década de 1960, fueron prescritas de forma amplia e irrestricta; el desarrollo posterior de fenómenos de tolerancia y abstinencia desatados por su uso prolongado restringió enérgicamente su empleo, a veces por debajo de las reales necesidades clínicas. Aunque las BZD están incluidas en el grupo IV de sustancias controladas de la Agencia de Control de Drogas (DEA) de los Estados Unidos de América, se acepta que, en general, no son drogas primarias de abuso, y los fenómenos adictivos relacionados con su uso requieren factores adicionales de riesgo tales como comorbilidad con otras drogodependencias. Es necesario distinguir entre casos de "uso inapropiado" de las BZD y aquellos que presentan criterios de franca dependencia. De hecho, se han reportado pocos casos de uso inapropiado de BZD prescritas por vía parenteral. Se presenta y discute el de una mujer de 51 años que, por un tiempo prolongado, acudió a emergencia psiquiátrica debido a crisis de disforia y ansiedad (no de pánico), recibiendo en varias oportunidades inyecciones intravenosas de diazepam, al punto que empezó luego a acudir reiteradamente para exigir la medicación sin que fuera médicamente necesaria. Es conveniente, por lo tanto, que el profesional que prescriba BZD parenterales, lo haga cautelosamente a fin de prevenir un proceso adictivo que puede generar serias consecuencias.

SUMMARY Benzodiazepines (BZDs) are essential drugs used in the treatment of different health problems: Peru's National Drug Petitionary lists five of them allowed for oral or parenteral administration. At the beginning in the 1960s, BZDs were widely and unrestrictedly prescribed; the subsequent development of tolerance and withdrawal phenomena, triggered by their prolonged use, led to drastic prescription restrictions, sometimes below the real clinical needs. Although BZDs are included in the Drug Enforcement Administration (DEA) group IV of controlled substances, it is accepted that, in general, they are not primary drugs of abuse, and the development of addictive phenomena only occurs in the presence of comorbidity with other drug addictions. It is necessary to distinguish between the "inappropriate use" or "misuse" of the BZDs and those cases that meet criteria of full dependence. There are few reported cases of inappropriate use of BZD prescribed by parenteral route. The case reported here is one of a 51-years-old woman who, over the course of several years, went to a psychiatric emergency service due to crisis of dysphoria and anxiety (but not a panic attack), and received on several occasions, intravenous injections of diazepam, to the point that later she used to go repeatedly to demand such medication, without being medically necessary. It is, therefore, important for the prescribing professional to use parenteral BZDs cautiously and carefully, in order to prevent an addictive process that can generate serious consequences.

Comparison of the sedative and anti-anxiety effects of levo-tetrahydropalmatine and diazepam on rats with conditioned fear / 中华行为医学与脑科学杂志

Objective:To compare the sedative and anti-anxiety effects of levo-tetrahydropalmatine (L-THP) and diazepam on conditioned fear model rats.Methods:According to the random number table method, 32 adult male rats were divided into blank group, model group, diazepam group and L-THP group(with 8 rats in each group). The conditioned fear model was reproduced by the plantar electric shock method. Four days after the modeling, the rats in diazepam group and L-THP group were given diazepam (3.6 mg/kg) and L-THP (25 mg/kg) were respectively gavaged once a day for 10 days, the rats in blank group and model group were given the same volume of saline. After the administration, the elevated plus maze test and the open field test were used to measure the anxiety behavior of the rats, and the sleep energy monitoring system was used to detect changes in sleep and energy-related indicators. SPSS 23.0 and Graphpad Prism 7.0 softwares were used for data analysis, multiple samples between groups were compared by one-way ANOVA, and LSD test was used for pairwise comparison.Results:The results of the elevated plus maze experiment showed that compared with the model group, the percentage of open-arm entry times ((11.27±8.78)%, (30.11±14.59)%, P<0.05) and the percentage of open-arm residence time ((1.94±1.48)%, (17.53±8.21)%, P<0.05) in diazepam group were all significantly increased. Compared with the model group, the open arm residence time, the percentage of open arm residence time and the percentage of open arm entry times in L-THP group showed an upward trend, but there was no statistical significance (all P>0.05). The results of the open field experiment showed that compared with the model group, the time of entering the central grid ((2.99±1.83) s, (6.94±3.52) s, P<0.05) and the time of entering the peripheral field ((297.01±1.83) s, (293.30±3.52) s, P<0.05) in diazepam group both increased. Compared with the model group, there was no significant difference in the changes of various indexes in L-THP group (all P>0.05). The results of locomotor activities showed that the autonomic activity times of model group in nighttime was significantly lower than that of blank group((758.79±375.37)times/h, (1 101.93±525.96)times/h, P<0.05). Compared with the model group, the number of autonomous activities of rats in L-THP group in daytime ((820.57±364.60) times/min, (502.40±228.54)times/min, P<0.05) decreased, and the number of autonomous activities in the nighttime ((758.79±375.37) times/min, (1 146.85±309.69)times/min, P<0.05) increased, but there was no significant change in the number of autonomous activities in the whole day. Correlation analysis of energy metabolism related indexes and sleep time of rats in each group were analyzed. The experimental results showed that the daytime sleep time were negatively correlated with heat value ( r=-0.335, P<0.05), and the night sleep time was positively correlated with daytime heat value ( r=0.352, P<0.05). Conclusion:L-tetrahydropalmatine has no significant anti-anxiety effect in the concentration range used in this study, but its sedative and improving sleep activity rhythm are better than diazepam.

Safety and efficacy of buccal midazolam compared to rectal diazepam for the acute treatment of seizures in children: A meta-analysis

OBJECTIVE@#To compare the safety and efficacy of buccal midazolam as opposed to rectal diazepam in the treatment of acute seizures in children less than 18 years old.@*METHODOLOGY@#This is a meta-analysis of randomized controlled trials comparing the use of buccal midazolam and rectal diazepam as treatment for acute seizures in children less than 18 years old. The total population of each study are as follows: 330 patients (Mpimbaza, 2008), 43 patients (Baysun, 2005), and 17 patients, all less than 18 years old, coming into the emergency department due to seizures.@*RESULTS@#There is no significant difference in the mean duration of seizure in minutes and seizure cessation in ten minutes between the buccal midazolam and rectal diazepam groups (Mean difference 0.39; 95% Confidence interval [CI] -0.18 to 0.96; p=0.17; Risk ratio [RR] 0.99; 95% CI 0.83 to 1,19, p=0.2). There is no significant difference in the risk of respiratory depression between buccal midazolam and rectal diazepam (RR 0.96; 95% CI 0.22 to 4.13; p=0.61).@*CONCLUSION@#The administration of buccal midazolam and rectal diazepam are similar in terms of efficacy and safety in terms of time to seizure cessation, termination of seizure within ten minutes, and risk of respiratory depression.

High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers / Dos pacientes que tomaban inductores necesitaron dosis altas de medicamentos metabolizados en gran medida por el CYP3A4 para alcanzar concentraciones terapéuticas

ABSTRACT Introduction: In the last 20 years of clinical practice, the senior author has identified these 2 rare cases in which the patients needed extremely high doses of drugs metabolized by CYP3A4 to reach and maintain serum therapeutic concentrations. Methods: The high metabolic ability of these 2 patients was demonstrated by the low concentration-to-dose ratios (C/D ratios) of several drugs metabolized by CYP3A4. Results: Case 1 was characterized by a history of high carbamazepine doses (up to 2,000 mg/day) and needed 170 mg/day of diazepam in 2 days to cooperate with dental cleaning. The high activity of the CYP3A4 isoenzyme was manifested by fast metabolism for quetiapine and diazepam, which took more than 1 year to normalize after the inducer, phenytoin, was stopped. Case 2 was also very sensitive to CYP3A4 inducers as indicated by very low C/D ratios for carbamazepine, risperidone and paliperidone. The carbamazepine (2,800 mg/day) and risperidone (20 mg/day) dosages for this second patient are the highest doses ever seen for these drugs by the senior author. Risperidone induction appeared to last for many months and metabolism was definitively normal 3 years after stopping carbamazepine. On the other hand, olanzapine C/D ratios were normal for induction. Conclusions: The literature has never described similar cases of very high doses of drugs metabolized by CYP3A4. We speculate that these 2 patients may have unusual genetic profiles at the nuclear receptor levels; these receptors regulate induction of drugs.

RESUMEN Introducción: Durante sus últimos 20 años de práctica, el último autor ha identificado estos 2 infrecuentes casos que necesitaban dosis extremadamente altas de medicaciones metabolizadas por el CYP3A4 para alcanzar y mantener concentraciones séricas terapéuticas. Métodos: La gran capacidad metabólica de estos 2 pacientes se demostró por los bajos cocientes entre concentración y dosis (C/D) de varias medicaciones metabolizadas por el CYP3A4. Resultados: El caso 1 se caracterizaba por una historia de altas dosis de carbamazepina (1.500 mg/día) y la necesidad de tomar 170 mg de diazepam en 2 días para facilitar una limpieza dental. La gran actividad de la isoenzima CYP3A4 se manifestó por una gran capacidad metabólica de quetiapina y diazepam, cuya normalización tardó más de 1 año tras la toma de un inductor, fenitoína. El caso 2 tambien era muy sensible a la inducción, lo cual se demuestra por los bajos cocientes C/D de carbamazepina, risperidona y paliperidona. Las dosis de carbamazepina (2.800 mg/día) y risperidona (20 mg/día) de este segundo paciente son las más altas nunca vistas por el último autor. La inducción de risperidona duró muchos meses y su metabolismo era normal 3 años después de interrumpir la carbamazepina. El cociente C/D de olanzapina era normal para la inducción. Conclusiones: Nunca se habían descrito casos similares de dosis tan altas de medicaciones metabolizadas por el CYP3A4. Se especula con que estos pacientes podrían tener unos perfiles genéticos inusuales en los receptores nucleares que regulan la inducción de medicamentos.

Effects of Oral Diazepam or Inhalatory Nitrous OxideOxygen for Conscious Sedation During Third Molar Surgery: A Randomized Controled Trial, Split Mouth Design / Efectos del Diazepam Oral o la Inhalación de Óxido Nitroso-Oxígeno para la Sedación Consciente Durante la Cirugía del Tercer Molar: Un Ensayo Controlado Aleatorio, Diseño de Boca Dividida

ABSTRACT: Anxiety in dental surgery may lead to behavioral and physiological changes for the patient and constitute a frequent challenge for the oral surgeon. The objective of this study was to compare the effect of inhalatory nitrous oxide and oxygen (N2O/O2) with oral diazepam conscious sedation in vital signs of patients undergone third molar extraction. Outpatients who needed removal of partially impacted, bilateral lower third molars, during the period of one year, were included. Each patient underwent conscious sedation with either oral diazepam or inhalatory N2O/O2 on a randomized controlled trial, split-mouth design. Systolic and diastolic blood pressure, heart rate and oxygen blood saturation were the changes measured before, at the beginning and the end of the procedure. Also, surgical procedure duration was recorded. Data from vital signs were submitted to analysis of variance and the duration of the surgery to paired Student's t-test. Twenty-five healthy outpatients (13 women and 12 men) with a mean age of 21.6 years were studied. There was an increase in systolic and diastolic pressure and in heart rate in the beginning; these values decreased and stabilized at the end of the surgical procedure in both treatments (p < 0.001) being lower in N2O/O2 but without difference between treatments. The surgical procedure duration was lower and occurred an expected increase of oximetry under N2O/O2 sedation (p < 0.001). Both treatments were effective for the conscious sedation but N2O/O2 showed better outcomes, mainly in duration of the surgery.

RESUMEN: La ansiedad en la cirugía dentoalveolar puede conducir a alteraciones fisiológicas y de comportamiento en el paciente, constituyendo así un desafío frecuente para el cirujano maxilofacial. El objetivo de este estudio fue comparar el efecto del óxido nitroso inhalatorio con oxígeno (N2O/O2) y la sedación consciente oral con diazepam por médio de los signos vitales de pacientes sometidos a la extracción del tercer molar. Fueron incluídos pacientes ambulatoriales com necesidad de exodoncia de terceros molares inferiores bilaterales, parcialmente impactados, durante el período de un año. Cada paciente fue sometido a sedación consciente con diazepam oral o N2O/O2 por inhalación en un ensayo controlado aleatorio, diseño de boca dividida. La presión arterial sistólica y diastólica, la frecuencia cardíaca y la saturación de oxígeno en la sangre fueron medidos antes, al inicio y al final del procedimiento. Además, se registró la duración del procedimiento quirúrgico. Los datos de los signos vitales fueron enviados para análisis de varianza y la duración de la cirugía para la prueba t de Student pareada. Se estudiaron 25 pacientes ambulatorios sanos (13 mujeres y 12 hombres) con una edad media de 21,6 años. Al início hubo un aumento en la presión sistólica y diastólica y en la frecuencia cardíaca; estos valores disminuyeron y se estabilizaron al final del procedimiento quirúrgico en ambos tratamientos (p <0,001), siendo más bajos en N2O/ O2 pero sin diferencia entre los tratamientos. La duración del procedimiento quirúrgico fue menor y se produjo un aumento esperado de la oximetría bajo sedación con N2O/O2 (p <0,001). Ambos tratamientos fueron efectivos para la sedación consciente, pero el N2O/O2 mostró mejores resultados, principalmente en la duración de la cirugía.

Effectiveness of Midazolam Compared to Diazepam and Placebo For Reducing Anxiety after Premedication at Sylhet Women’s Medical College

Introduction: Anxiolytic premedication is debated most of thetime in the outpatient surgical community. The management ofanxiety reducing medications may be considered unnecessaryby anesthesiologists when anxiety rates are small inoutpatients with minor operations. Thanks to its rapid onsetand short halflife, intravenous (IV) midazolam is the mostwidely used premedicant in ambulatory environments, but itspersistent effects in the prompt postoperative period may leadto postoperative sedation, as well as delayed recovery anddischarge readiness after brief ambulatory surgery.Objective: This research is carried out specifically to checkwhether the use of the medicine for preanesthesia midazolamquantifiably decreases pain as opposed to having nopreanesthesia drug (placebo) or diazepam prior to medicalprocedures.Method: The examination's inclusion requirements arepatients aged between 18 and 68 years scheduled for electivesurgery or diagnostic procedures involving anesthesia. Aninterventional (clinical trial) study with 160 patients scheduledfor surgical or diagnostic procedures involving anesthesiatechniques was performed at a neighbourhood emergencyclinic called Sylhet Women’s Medical College located in Sylhet,Bangladesh. Research length from Aug 2018 to Aug 2019.Results: After multiple investigations of knowledge andanalysis it was discovered that diazepam with little or nosymptoms placed ahead of midazolam and placebo.Conclusion: It can be clearly inferred that in case of adecrease in anxiety, diazepam ranks first compared tomidazolam or placebo.

Evaluation of antianxiety effect of cinnamaldehyde in swiss albino mice

Background: Cinnamon is one of the best known spices used as an herbal medicine. Cinnamaldehyde (CNM) the volatile oil, which was present in the essential oil of the bark, is the important constituents of cinnamon. Cinnamon has been investigated for its various effects like peptic ulcer protection, antioxidant property, inhibition of tau aggregation, anti-inflammatory activity, effect on cardiovascular system, anti-nociceptive activity, hepato-protective effects, hypolipidemic and antidiabetic activites. The present study was aimed to evaluate the anxiolytic effect of CNM per se and its interaction with diazepam in swiss albino mice.Methods: Anxiolytic activity was evaluated by elevated plus maze method. A group of 36 healthy mice of either sex weighing 20-30 grams were divided at random into six groups (n=6). CNM and diazepam were dissolved in tween twenty 20% to maintain uniformity of the solvent and given orally. Group I was given twenty 20% (10 ml/kg, p.o.), group II diazepam (0.5 mg/kg, p.o.), group III diazepam (1 mg/kg, p.o.), group IV cinnamaldehyde (100 mg/kg, p.o.), group V cinnamaldehyde (200 mg/kg, p.o.), group VI cinnamaldehyde and diazepam (100 mg/kg and 0.5 mg/kg, p.o.).Results: Cinnamaldehyde per se showed no anxiolytic effect at any dose (p<0.05). The standard drug diazepam has shown significant anxiolytic activity on elevated plus maze. Whereas combination of diazepam 0.5 mg/kg and cinnamaldehyde 100 mg/kg showed significant increase in the time spent in open arms as compared to all groups (p<0.05).Conclusions: CNM per se did not show any effect on anxiety but enhanced the action of diazepam when co-administered.

Antinociceptive activity of Thyme (Thymus vulgaris L. ) and interactions with neurotropics and analgesics

The plant world represents an important source of potential therapeutic agents, but concomitant administration of herbal and conventional medications may result in interactions with subsequent beneficial or adverse effects. This study was designed to examine the analgesic effect of thyme tincture and thyme syrup, two commonly used thyme formulations, and their interactions with codeine, paracetamol, pentobarbital and diazepam in mice. The identification and quantification of thymol and carvacrol were carried out by GC/MS and GC/FID. The analgesic activity was studied using a hot plate method. Effects of thyme syrup on diazepam-induced motor coordination impairment in rotarod test and on pentobarbital-induced sleeping time were also determined. Thymol (175.3 µg/mL and 9.73 µg/mL) and carvacrol (10.54 µg/mL and 0.55 µg/mL) concentrations were measured in tincture and syrup, respectively. Thyme syrup and tincture exhibited effective analgesic activity in the hot plate pain model. Pretreatment with thyme formulations reduced analgesic activity of codeine, and potentiated the analgesic activity of paracetamol. Co-administration of thyme formulations has led to potentiation of diazepam and pentobarbital depressive central nervous system effects. Thyme formulations interacted with tested conventional drugs, probably through interference with their metabolic pathways and succeeding altered concentrations and pharmacological effects.

Evaluation of anxiolytic properties of BacoMind extract of plant Bacopa monnieri Linn. in comparison with diazepam in rodent model

Background: Anxiety is a state characterized by somatic, emotional, cognitive, and behavioral components, associated with significant disability. The pharmacotherapy for anxiety remains limited for achievable safety and tolerability of the medicines. Benzodiazepines use associated with side effects like psychomotor impairment and addiction liability. Due to the ADRs associated with antianxiety drugs, the drug trials have focused on screening herbal medicines that are reportedly used in the treatment of anxiety and which have minimal side effects.Methods: The anxiolytic activity was examined by using the elevated plus maze (EPM) and open field test (OFT), forty Albino wistar strain rats of both sex of weighing 120 to 200 g were divided into four groups of ten rats each.. Group 1 received vehicle (normal saline); group 2 received diazepam (1 mg/kg); groups 3 and 4 received BacoMind�, 30 and 60 mg/kg oral, respectively.Results: Rats treated with diazepam (1 mg/kg, p.o.) showed significant (p<0.001) increase in the percentage of open arms entries and time spent whereas, in closed arm the number of entries and time spent were significantly (p<0.05) decreased. Intraperitonial administration of BacoMind� extract of plant Bacopa monnieri Linn. exhibited significant (p<0.05) increase in the number of open arm entries and time spent with significant (p<0.05) reduction in number of entries and time spent in the closed arm as compared to group 1. BacoMind� treated rats also produced significant increase in the number of rearings (p<0.05), assisted rearings and number of squares crossed (p<0.01).Conclusions: BacoMind� extract of plant Bacopa monnieri Linn possess significant anxiolytic activity in the rats. It can be a promising anxiolytic agent.

A study to evaluate the skeletal muscle relaxant property of Pregabalin and Gabapentin in albino rats

Background: Skeletal muscle relaxants are the drugs which reduce unwanted spasm without interfering with consciousness and voluntary movements. The centrally acting muscle relaxants like Diazepam, is known to be GABA mimetics and other antiepileptics like Gabapentin and Pregabalin also act through the release of GABA. This study is done to investigate skeletal muscle relaxant property of these drugs in comparison to Diazepam.Methods: T Models used in the experiment are Grip Strength Test, Rota Rod Method, Beam Walk Test, Photoactometer Test. Animals were divided into 6 groups of 6 rats each: Group 1: Control group treated with normal saline (0.1 ml/10gm), Group 2: Standard-15mg/kg of Diazepam, Group 3:T1-60 mg/kg of Gabapentin, Group 4:T2-10 mg/kg of Pregabalin, Group 5:T3-60 mg/kg of Gabapentin+Diazepam, Group 6:T4- 10 mg/kg of Pregabalin+Diazepam. Mean and standard deviation was calculated for each group. One way ANOVA was used for multiple group comparisons followed by post hoc Tukey’s test for statistical significance between the groups.Results: Treatment with the above test drugs produced significant muscle relaxation and caused decreased fall off, sliding time, increase climbing time and decreased locomotor activity in all models indicating motor incoordination. The results obtained from both standard and test groups showed a highly significant difference in muscle relaxation when compared with the control group.Conclusions: The test drugs showed skeletal muscle relaxant property in rats comparable to Diazepam. In view of these results, it can open a new avenue for these drugs to be used as skeletal muscle relaxants after conducting clinical trials.

Benzodiazepine premedication in general anaesthesia: a clinical comparative study

Background:The main aims of pre-anaesthetic medication are anxiolysis, analgesia, anti-emesis and reducing perioperative patient risk. Producing a state of amnesia for pre and post-operative events is desired by all. This study has been undertaken to evaluate the role of three of the benzodiazepines i.e. diazepam, lorazepam and midazolam during general anaesthesia, in providing anxiolysis, sedation and amnesia.Methods:The study included patients with ASA grade I and ASA grade II physical status of both sexes, age ranging between 18-60 years. Patients were divided into three groups of thirty patients each, every group receiving intramuscular injections of diazepam 0.1 mg/kg body weight, lorazepam 0.07 mg/kg body weight and midazolam0.08 mg/kg body weight respectively; 45 minutes prior to induction of general anaesthesia. Anxiety assessment before premedication along with assessment of sedation after premedication was done.Results:Before premedication the mean values of pulse rate, blood pressure and respiratory rate were not significantly different among the three groups (p>0.05). Maximum changes in these parameters were observed with Midazolam followed by lorazepam and diazepam. The dose of thiopentone used as inducing agent was also lowered significantly in case of midazolam (p<0.05). One patient in midazolam group showed respiratory depression whereas four patients receiving lorazepam and diazepam showed delayed recovery and prolonged sedation, but the effects were self-limiting. Conclusions: Midazolam offers the maximum advantage in allaying anxiety and providing excellent sedation and amnesia during general anaesthesia and proves to be the most suitable premedicant before general anaesthesia.

Evaluation of centrally acting skeletal muscle relaxant activity of aqueous extract of Withania somnifera (ashwagandha) roots in albino mice

Background: Skeletal muscle relaxants are used to treat both muscle spasm and spasticity, acting both as antispasmodic and antispasticity agents. In past studies some polyherbal formulations containing ashwagandha have shown skeletal muscle relaxant activity and fat extract of ashwagandha showed skeletal muscle relaxant activity in experimental animal models. This study is designed to evaluate the skeletal muscle relaxant activity of aqueous extract of Withania somnifera (ashwagandha) roots in albino mice, as the literature regarding them is limited.Methods: Standard drug (diazepam) and different doses of Aqueous extract of ashwagandha (50, 100,150mg/kg) were given orally to albino mice. Skeletal muscle relaxant activity was assessed by Rota-rod apparatus. The fall off time from the rotating rod was noted for each group after 1 hour of drug administration. The difference in fall off time from the rotating rod between the standard and treated mice was taken as an index of muscle relaxation.Results: The test extract at doses (50mg/kg, 100mg/kg and 150mg/kg) showed highly significant reduction in the time spent by the animals on revolving rod in rota rod test when compared to baseline (p <0.0001). As compared with diazepam, aqueous extract (150mg/kg) showed almost equal reduction in the time spent by the animals on revolving rod in rota rod test.Conclusions: This study indicates that the aqueous extract of ashwagandha possess central skeletal muscle relaxant activity. The results are promising for further investigation of efficient skeletal muscle relaxant activity.

Effect analysis of diazepam combined with phenobarbital in the treatment of febrile convulsions in children / 中国基层医药

To investigate the clinical effect of diazepam combined with phenobarbital in the treatment of febrile convulsions in children.Methods From January 2015 to July 2017,100 children with febrile convulsions in the Women＇s and Children＇s Hospital of Ningbo were selected and divided into two groups by random number table,with 50 cases in each group.The control group was treated with diazepam ,while the observation group was treated with diazepam combined with phenobarbital.The clinical efficacy,anticonvulsive time,myocardial enzyme index,hypersensitive C-reactive protein and incidence of adverse reactions were compared between the two groups . Results (1)The total clinical effective rate of the observation group (98%) was higher than that of the control group (χ2 ＝4.891,P＜0.05),and the time of stopping convulsion [(20.92 ±4.49) min] was shorter than that of the control group(t＝5.443,P＜0.05).(2) After treatment,the creatine kinase isoenzymes [(25.93 ±12.76) U／L], phosphocreatinase [(189.47 ±7.35 ) U／L], hydroxybutyrate dehydrogenase [( 276.73 ±12.85 ) U／L ], lactate dehydrogenase[(305.94 ±13.27)U／L],hypersensitive C-reactive protein[(5.04 ±1.65)ng／L] in the observation group were lower than those in the control group (t＝4.961,5.333,5.901,6.160,5.354,all P＜0.05).(3) During the treatment period, no obvious adverse reactions occurred in both two groups.Conclusion The combination of diazepam and phenobarbital can effectively arrest febrile convulsions in children ,improve the clinical efficacy ,protect myocardial cells,it has fewer adverse reactions ,it is safe and reliable.

Effect analysis of diazepam combined with phenobarbital in the treatment of febrile convulsions in children / 中国基层医药

Objective@#To investigate the clinical effect of diazepam combined with phenobarbital in the treatment of febrile convulsions in children.@*Methods@#From January 2015 to July 2017, 100 children with febrile convulsions in the Women's and Children's Hospital of Ningbo were selected and divided into two groups by random number table, with 50 cases in each group.The control group was treated with diazepam, while the observation group was treated with diazepam combined with phenobarbital.The clinical efficacy, anticonvulsive time, myocardial enzyme index, hypersensitive C-reactive protein and incidence of adverse reactions were compared between the two groups.@*Results@#(1)The total clinical effective rate of the observation group(98%) was higher than that of the control group(χ2=4.891, P<0.05), and the time of stopping convulsion[(20.92±4.49)min] was shorter than that of the control group(t=5.443, P<0.05). (2)After treatment, the creatine kinase isoenzymes[(25.93±12.76)U/L], phosphocreatinase[(189.47±7.35)U/L], hydroxybutyrate dehydrogenase[(276.73±12.85)U/L], lactate dehydrogenase[(305.94±13.27)U/L], hypersensitive C-reactive protein[(5.04±1.65)ng/L] in the observation group were lower than those in the control group(t=4.961, 5.333, 5.901, 6.160, 5.354, all P<0.05). (3)During the treatment period, no obvious adverse reactions occurred in both two groups.@*Conclusion@#The combination of diazepam and phenobarbital can effectively arrest febrile convulsions in children, improve the clinical efficacy, protect myocardial cells, it has fewer adverse reactions, it is safe and reliable.

Effects of Glycyrrhizic Acid on Pharmacokinetics of Nifedipine in Rats / 中国药房

OBJECTIVE： To study the effects of glycyrrhizic acid on the pharmacokinetics of nifedipine in rats. METHODS： Rats were randomly divided into experimental group and control group， with 10 rats in each group. Experimental group was given glycyrrhizic acid 5 mg/kg and control group was given 0.5％ CMC-Na （sodium carboxymethylcellulose） solution， once a day， for 14 consecutive days. On 14th day after 30 min of intragastric administration， both groups were given nifedipine 3 mg/kg intragastrically. Blood samples 0.5 mL were collected from intraocular vein plexus before and at 0.25， 0.5， 0.75， 1， 1.5， 2， 3， 4， 6， 8， 12 and 24 h after intragastric administration. The concentration of nifedipine was determined by HPLC using diazepam as internal standard. The determination was performed on ODS-C18 column with mobile phase consisted of methanol-water （62 ∶ 38，     V/V，pH adjusted to 4.5 with acetic acid） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃. The detection wavelength was set at 238 nm， and sample size was 20 μL. The pharmacokinetic parameters were calculated with Winonlin 6.0 software， and statistical analysis was performed by t-test. RESULTS： The main pharmacokinetic parameters of the experimental group and the control group were as follows as tmax was （1.40±0.15）， （1.50±0.01） h； cmax was （0.15±0.03）， （0.29±0.09）      mg/L； t1/2 was （4.70±1.17）， （5.20±1.38） h； AUC0-24 h were （1.00±0.10）， （1.89±0.37） mg·h/L； AUC0-∞ was （1.00±0.16）， （1.98±0.32） mg·h/L； MRT was （6.76±0.64）， （6.60±1.36） h， respectively. Compared with control group， cmax， AUC0-24 h and AUC0-∞ of nifedipine were decreased significantly in experimental group， with statistical significance （P＜0.05）. CONCLUSIONS： Glycyrrhizic acid can reduce the bioavailability of nifedipine in rats. It is suggested that the dosage of nifedipine should be increased in order to achieve effective blood concentration.

Ion Abundance Ratios of Qualitative Analysis by GC-MS of 4 Common Drugs （Poisons / 法医学杂志

Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs （poisons） in blood by gas chromatography-mass spectrometry （GC-MS） method. Methods Four common drugs （poisons） （dichlorvos, phorate, diazepam and estazolam） were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs （poisons） in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 μg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection （LOD）, 2LOD, limit of quantitation （LOQ） and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs （poisons） and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant （P>0.05）. More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration （concentration less than 2LOQ） or low signal to noise ratio （3-15）, the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs （poisons） in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.

Effect of promethazine on seizure activity and its interactions with antiepileptic drugs diazepam and phenytoin in Rats

Background: Current antiepileptic drugs (AEDs) are effective in controlling seizures in about 70% patients but use is often limited by adverse effects. Promethazine, H1 receptor antagonist, has a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs in rats.Methods: The effect of promethazine (10mg/kg) and its interactions with antiepileptic drugs diazepam and phenytoin was assessed by using maximal electroshock seizures (MES) and chemoshock (PTZ) method.Results: Promethazine along with diazepam in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.Conclusions: Subtherapeutic doses of Promethazine alone and in combination with diazepam showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method suggesting histamine plays a protective role in development of seizures. This shows dual behavior of promethazine on MES and PTZ induced seizures.