Cytotoxicity evaluation of haloperidol, clozapine and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells

Abstract Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 µM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 µM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 µM) and CLO (0.01 and 1 µM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 µM. HAL and CLO present cytotoxicity at 0.1 µM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics

Homocysteine Levels and Clinical Outcomes in Schizophrenia—A Pilot Randomized Controlled Trial

Objectives: To find out the relation between homocysteine levels in peripheral blood and the effectiveness as well as the safety of haloperidol and olanzapine in schizophrenia treatment. Materials and Methods: A prospective randomized parallel-group open-label interventional clinical trial was conducted on 40 mild to moderate schizophrenia patients. To compare the efficacy of olanzapine and haloperidol Brief Psychiatric Rating Scale (BPRS) score was used. Homocysteine levels of peripheral blood and Abnormal Involuntary Movement Scale scores were evaluated. Results: BPRS score improved in both groups on day 14 and day 28. But significantly more with olanzapine (P value =.001). The olanzapine group showed a higher reduction (13.91±0.47 to 9.74±0.5) in homocysteine levels than the haloperidol group. Also, the BPRS scores negatively correlated (r = –0.66) to homocysteine levels. Conclusion: Therefore, our study shows that peripheral blood homocysteine levels can be used to predict and assess the treatment outcome in schizophrenia patients. Biomarker driven approach in schizophrenia will allow the patients to be treated promptly with the right drug. In this light, personalized treatment holds great potential in the future.

Esquizofrenia asociada a consumo de múltiples sustancias. Responsabilidad profesional / Schizophrenia Associated with Multiple Substance Use

Resumen La esquizofrenia es un trastorno psiquiátrico grave clasificado dentro de los trastornos psicóticos. Los pacientes suelen presentar síntomas variables dependiendo de las 3 dimensiones sintomáticas que padezcan, lo que genera dilación en su apego temprano al tratamiento. El caso clínico de interés a presentar corresponde a un paciente del sexo masculino en la cuarta década de la vida diagnosticado con esquizofrenia asociado al consumo de múltiples sustancias, el cual fue motivo de analizar derivado de los efectos adversos presentados al tratamiento farmacológico posterior a un episodio psicótico. El abordaje farmacológico con pacientes que padecen esta patología debe ir encaminado a contrarrestar los síntomas con base en antipsicóticos y a los efectos adversos causados por los mismos, siempre y cuando la enfermedad sea diagnosticada oportunamente.

Abstract Schizophrenia is a severe psychiatric disorder classified within the psychotic disorders. Patients usually present variable symptoms depending on the three symptomatic dimensions they suffer from, which generates delay in their early adherence to treatment. The clinical case of interest to be presented corresponds to a male patient in the fourth decade of life diagnosed with schizophrenia associated with multiple substance use, which was analyzed due to the adverse effects of pharmacological treatment following a psychotic episode. The pharmacological approach with patients suffering from this pathology should be aimed at counteracting the symptoms based on antipsychotics and the adverse effects caused by them as long as the disease is diagnosed in a timely manner.

Psicosis por consumo de ayahuasca: un reporte de caso / Ayahuasca-Induced Psychosis: A Case Report

RESUMEN La inducción de psicosis por ayahuasca es un evento poco frecuente. Sin embargo, debido a un aumento en el acceso y la distribución de esta sustancia, resulta menester destacar los casos en que se presenta. Se describe el caso de un paciente varón de 26 arios que ingresó al servicio de psiquiatría por un cuadro clínico de 7 meses de evolución dado por cambios en el comportamiento, ideas delirantes y posterior exacerbación de los síntomas, tras participar en una ceremonia ritual en la que consumió por vez primera un brebaje de ayahuasca. Requirió inicialmente tratamiento hospitalario para controlar el episodio psicótico agudo, con buena respuesta y tolerancia al tratamiento farmacológico, lo que permitió continuar su seguimiento clínico ambulatorio.

ABSTRACT Psychosis induced by ayahuasca is a rare occurrence. However, due to an increase in the access and distribution of this substance, it is necessary to highlight the cases in which it occurs. We describe the case of a 26-year-old man who was admitted to the psychiatric service after seven months of changes in behaviour, delusions and the subsequent exacerbation of symptoms, after participating in a ritual ceremony during which he consumed an ayahuasca concoction for the first time. Initially, he required hospital treatment to control the acute psychotic episode, but after tolerating and responding well to the antipsychotic treatment, he was discharged with an outpatient follow-up.

Glyceryl behenate-based solid lipid nanoparticles as a carrier of haloperidol for nose to brain delivery: formulation development, in-vitro, and in-vivo evaluation

Abstract This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.

Angioedema com haloperidol: um relato de caso / Angioedema with haloperidol: a case report

O haloperidol é um antipsicótico de primeira geração e um dos medicamentos mais usados dentro dessa categoria. É um potente antagonista de ação central dos recetores de dopamina tipo 2, com baixa atividade anti alfa 1 adrenérgica e sem atividade anti-histamínica ou anticolinérgica, regularmente utilizado em casos de agitação. O angioedema é um efeito colateral especialmente grave, caracterizado por edema acentuado do tecido subcutâneo ou submucoso, e pode afetar várias partes do corpo, podendo até culminar, nos casos mais graves, em morte. Já foi descrito com administração de vários antipsicóticos, como clozapina, risperidona, ziprazidona e clorpromazina, no entanto é raro como resultado da administração de haloperidol, ocorrendo em <1% dos casos. O objetivo deste artigo é descrever o desenvolvimento de angioedema em um paciente com síndrome confusional agudo após a segunda administração de haloperidol IM para controle sintomático da agitação em contexto de serviço de urgência. [au]

Haloperidol is a first-generation antipsychotic and one of the most commonly used drugs within this category. It is a potent centrally acting antagonist of type 2 dopamine receptors, with low anti-alpha-1-adrenergic activity and no antihistaminic or anticholinergic activity, regularly used in cases of agitation. Angioedema is an especially serious side effect, characterized by marked edema of the subcutaneous or submucosal tissue, and can affect various parts of the body, and may even culminate, in the most severe cases, in death. It has already been described with the administration of several antipsychotics, such as clozapine, risperidone, ziprasidone, and chlorpromazine, but it is rare as a result of administration of haloperidol, occurring in <1% of cases. This article aims to describe the development of angioedema in a patient with acute confusional syndrome after the second administration of IM haloperidol for symptomatic control of agitation in an emergency department setting. [au]

The mechanism of antipsychotics interfering with schizophrenic-like phenotype in early social isolation mice / 西安交通大学学报(医学版)

【Objective】 To investigate and compare the effects and mechanisms of risperidone and haloperidol on early socially isolated mice. 【Methods】 C57BL/6 mice aged 3 weeks were raised in single cages after weaning for social isolation （SI）， and the control （GH） group was raised normally. Eight weeks later （mouse adult）， the mice received intraperitoneal injection of equal volumes of normal saline （NS）， risperidone （RIS） and haloperidol （HA）. Then they were divided into four groups： GH+NS， SI+NS， SI+RIS， and SI+HA. The dose of risperidone and haloperidol was 0.1 mg/kg and 0.2 mg/kg， respectively. After administration for 14 days， through the open field experiment， elevated plus maze experiment， forced swimming experiment， nesting experiment， social interaction experiment， novel object discrimination experiment， and prepulse suppression experiment， the mice’s schizophrenia-like behavior was evaluated in terms of autonomous activities， emotions， cognition， and social behavior. We also detected dopamine type 2 receptor （D2R） and the N-methyl-D-aspartate receptor subunit NR1 in the prefrontal cortex （PFC） and nucleus accumbens （NAc）. 【Results】 Compared with those in GH group， the anxiety-like behavior and depression-like behavior of SI mice were significantly increased （P<0.05）， while the nesting ability was significantly decreased （P<0.05） and social interaction and avoidance behavior were significantly reduced （P<0.05）； the cognitive function of PPI was impaired （P<0.05）. Compared with haloperidol， risperidone improved not only depression-like behavior and PPI impairment， but also anxiety-like behavior， nesting ability， social interaction， and avoidance behavior. In SI+RIS and SI+HAL groups， the content of D2R in NAC decreased significantly， and the difference of NR1 in PFC disappeared compared with the control group. 【Conclusion】 Early SI is a good model for simulating schizophrenia. Risperidone has a better intervention effect than haloperidol； risperidone and haloperidol may exert their effects through D2R and NR1.

Clozapine prescribing patterns in hospitalised patients in everyday clinical practice

Aim: Clozapine is the gold standard for treatment-resistant schizophrenia. Despite clear recommendations for use, under-use and excessive delay in the use of clozapine are an ongoing findings in the literature. The aim of this study was to analyse the clozapine prescribing patterns in hospitalised patients in everyday clinical practice in Serbia. Methods: This cross-sectional study was conducted in Clinic for Mental Disorders “'Dr Laza Lazarevi?”' in Belgrade and included a sample of 238 patients, discharged from hospital treatment during 2018. Demographic, data on the clinical characteristics of the subjects, dosage and combination of clozapine with other psychopharmacs were collected retrospectively, from the patients’ medical records. Descriptive and statistical hypothesis testing methods were used to analyse the primary data. Results: The incidence of clozapine administration was 23.5%. Clozapine was introduced into therapy after average treatment duration of 7.2 years and prior administration of three different antipsychotics. 68.1% of patients were treated with dual antipsychotic therapy prior to clozapine administration. In 53.8% of patients, clozapine was prescribed as antipsychotic monotherapy, while only eight per cent were not prescribed adjuvant therapy. The most commonly used antipsychotic in combination with clozapine was haloperidol (34.9%), while the most prescribed non-antipsychotic adjuvant drug was valproate (66%). Benzodiazepines were prescribed in 55.9% of subjects. In most subjects, the dose of clozapine was less than the standard dose. Conclusion: Clozapine is prescribed less frequently than expected and is often used in an irrational manner. Additional research is needed to advance its application in everyday clinical practice.

Evaluation of the effects of donepezil in psychotic disorders using Swiss albino mice

Background: Schizophrenia as a psychotic disorder is currently treated by various antipsychotic drugs. A large group of patients still remain resistant to the treatment and present in the form of residual cognitive deficits. Donepezil has been advocated at various conferences and seminars for using it in schizophrenia patients. Donepezil is currently approved drug for Alzheimer's disease to improve cognition. Hence, we have tried to assess its role for psychotic models induced by methylphenidate in mice.Methods: Methylphenidate 5 mg/kg was given by intraperitoneal (i.p) route to induce psychosis in Swiss albino mice (n=6). Donepezil was given alone in a dose of 1 mg/kg and in combination with low dose haloperidol 0.1 mg/kg and groups were compared with haloperidol 0.2 mg/kg. Activity of donepezil was also assessed on the haloperidol induced catalepsy test. Statistical analysis was done with ANOVA followed by Bonferroni抯 test.Results: Methylphenidate successfully induced characteristic stereotypy behaviour in mice similar to amphetamine. Both donepezil 1 mg/kg and haloperidol 0.2 mg/kg showed significant reduction in stereotypy behaviour and there was no statistically significant difference between the two (p<0.05). Effects with donepezil were only slightly inferior to standard while it抯 combination (1 mg/kg with haloperidol 0.1 mg/kg) showed comparable results with the standard haloperidol. Donepezil had only marginally enhanced potential to induce catatonia which was statistically insignificant (p>0.05).Conclusions: Methylphenidate can be used successfully to induce psychosis in animals and donepezil may be a promising and potentially useful drug as add on therapy to routine antipsychotics.

Effect of methonolic extract of Vitex negundo on haloperidol induced catalepsy in albino mice

Background: Plants are being used in traditional medicine since history of mankind. The knowledge of these medicinal plants has accrued in the course of many centuries leading to medicinal systems in India such as Ayurveda, Unani and Siddha. Objective: In the present study, we evaluated the anticataleptic efficacy of Vitex negundo, a polyherbal formulation in haloperidol induced catalepsy in mice.Methods: Five groups (n=6) of male albino mice were used in the study. Catalepsy was induced by i.p. administration of haloperidol (1 mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of Vitex negundo (50, 100, 200 mg/kg) with standard received Pheniramine maleate 10 mg/kg, i.p.Results: In vehicle treated animals, haloperidol (1 mg/kg. i.p.) produced the maximum catalepsy at 180 min (46.78�78 min). Standard treated as Pheniramine maleate 10 mg/kg, i.p. shows maximum at 120 min. 19.24�32. Test herb, i.p. Methanolic extract of Vitex negundo (50, 100, 200 mg/kg, i.p.) significantly potentiated haloperidol induced catalepsy at each time interval, in a dose dependent manner. At dose 50, 100 and 200mg/kg, extract of Vitex negundo (Linn.) roots showed maximum cataleptic score 12.34�78, 14.43�43 and 15.43�67 min, respectively at 120 minutes in haloperidol treated animals.Conclusions: The present study indicates that the methanolic extract of Vitex negundo reduces haloperidol-induced catalepsy in mice.

A study on haloperidol and risperidone induced metabolic derangements in patients with newly diagnosed schizophrenia

Background: The occurrence of metabolic abnormalities in schizophrenic patients has been increased with the rampant use of second-generation antipsychotics. The aim and objective of this study is to compare the metabolic derangements induced by a typical antipsychotic: haloperidol and an atypical antipsychotic, risperidone in patients with newly diagnosed schizophrenia in a tertiary care hospital.Methods: Out of 60 newly diagnosed schizophrenic patients, 30 patients received tablet haloperidol and the remaining 30 patients received tablet risperidone orally. The anthropometric measurements like height, weight, waist circumference was measured and blood investigations like fasting blood glucose level and fasting lipid profile were taken at baseline and at the end of 3 and 6 months of drug therapy. The metabolic derangements induced by the two antipsychotics were compared and analyzed at end of 3rd and 6th month using SPSS software version 16.Results: At the end of 6th month statistically significant differences (p<0.05) were observed in weight, waist circumference, fasting blood sugar, fasting triglyceride and high-density lipoprotein level between the haloperidol and risperidone group on following the International Diabetic Federation (IDF) criteria of metabolic syndrome. Risperidone caused metabolic abnormalities in 13.3%, 4 patients whereas none of the patients in haloperidol group developed metabolic syndrome.Conclusions: Hence it is concluded that the atypical antipsychotic risperidone has been associated with an increased risk of causing metabolic abnormalities than the typical antipsychotic haloperidol. Regular and periodic monitoring of the anthropometric and metabolic parameters in schizophrenic patients on antipsychotics especially the atypical antipsychotics is mandatory to prevent further complications.

A Retrospective Study of the Incidence of Subcutaneous Induration Induced by Hydromorphone and Haloperidol

This retrospective study investigated the incidence of subcutaneous induration induced by hydromorphone citrate (HM) and haloperidol (HPD). From September 2018 to December 2019, 75 consecutive patients admitted to our palliative care unit were enrolled. A total of 177 subcutaneous injection sight reactions were assessed from the study initiation to data collection. Patients were then classified into three groups: group A, administered HM + normal saline (NS); group B, administered HM + HPD + NS; and group C, administered HM + HPD + 5% glucose water (Glu). Subcutaneous indurations were observed 29 times at the median of 71.0 (27–151) h. The incidence rates of subcutaneous induration were 4.7% (4/86), 39.1% (18/46), and 15.6% (7/45) in groups A, B, and C, respectively. A significant difference in this rate was observed between groups A and B and between groups B and C. The incidence rates of subcutaneous induration were low in the HM + NS group, but it rose by the addition of haloperidol significantly. Changing from NS to Glu as dilution liquid for HM + HPD decreased subcutaneous induration incidence.

Decreased Concentration of Hydromorphone Citrate in Subcutaneous Infusion Therapy Led to the Improvement of Subcutaneous Induration: A Case Report

We reported a clinical case in which decreased concentration of hydromorphone citrate in subcutaneous infusion therapy led to the improvement of subcutaneous induration. A subcutaneous infusion therapy with hydromorphone citrate was initiated in a 60-year-old female pancreatic-cancer patient with back pain. A subcutaneous induration has emerged when the infused concentration of hydromorphone citrate was increased from 0.17% to 0.83%. After the reduction in its concentration (0.28%), that subcutaneous induration has improved. For the alleviation of nausea and sedation, administration of haloperidol and midazolam were added at day 61 and day 70, respectively, with keeping the low concentration (≤0.28%) of hydromorphone citrate. Under this condition, further occurrence of subcutaneous induration was not observed. As a result, we suggested that the concentration of hydromorphone citrate in subcutaneous infusion therapy determined the onset of subcutaneous induration.

Subcutaneous Induration Induced by Haloperidol with Hydromorphone Citrate: A Case Report

We report that the discontinuation of haloperidol during subcutaneous infusion therapy with hydromorphone citrate led to the improvement of subcutaneous induration. A 70-year-old female was admitted to our palliative care unit with neck pain. She had neck lymph node metastasis from carcinoma of unknown origin. As subcutaneous infusion of hydromorphone citrate caused nausea, we administered haloperidol with hydromorphone citrate in normal saline. The infusion sites after 4, 9, and 11 days were changed because of subcutaneous induration, which we considered to be caused by haloperidol. After discontinuation of haloperidol, induration at the infusion site was not observed.

Efficacy of risperidone and haloperidol in treatment of schizophrenia in tertiary care hospital

Background: Schizophrenia is a chronic debilitating disease with significant morbidity and mortality that often requires either typical or atypical antipsychotic pharmacotherapy. Atypical antipsychotic drugs are preferred over typical because of lower risk of extra pyramidal side effects. As there is paucity of data in Indian population, the present study was taken up to evaluate the efficacy of haloperidol and risperidone in the treatment of schizophrenia.Methods: It was a comparative study conducted on 60 patients of Schizophrenia for one year in a tertiary care hospital. The study subjects were randomly assigned into 2 groups of 30 patients each, where group 1 were treated with atypical antipsychotic drug risperidone and group 2 with typical antipsychotic drug Haloperidol and both groups received the treatment for one year. Efficacy was measured using positive and negative syndrome scale (PANSS), clinical global impression - severity of illness (CGI-S), clinical global impression - improvement (CGI-I) scales.Results: Both haloperidol and risperidone were associated with comparable baseline to endpoint reduction in symptom severity. However, risperidone treated subjects had significantly greater decrease in symptom severity as measured by PANSS score and total score, CGI-S scale. However, there is no significant difference between two groups in terms of CGI-S score.Conclusions: The reduction in positive, negative and general scores in risperidone treated patients were significant with that of haloperidol treated patients.

Assessment of Morus alba (mulberry) leaves extract for anti-psychotic effect in rats

Background: Morus alba commonly known as white mulberry has been widely cultivated to feed silkworms. This widely grown plant has been in use by tribals of this country for ailments such as asthma, cough, bronchitis, edema, insomnia, wound healing, diabetes, influenza, eye infections and nose bleeds. Various parts of morus alba linn are used as an cardioprotective, hepatoprotective anti-inflammatory, hypoglycemic, free radical scavenging activity and neuro-protective agent. In this study, anti-psychotic property of M. alba leaves extract (MAE) was evaluated by Haloperidol induced catalepsy model in rats.Methods: In this study Haloperidol induced catalepsy model was used to evaluate antipsychotic effects in rats. Haloperidol (1 mg/kg) was injected intraperitoneally to rats (n=6) pretreated with vehicle (0.5 mg/kg, i.p.) or MAE (100, 200 and 400 mg/kg, i.p).Results: In control treated animals, haloperidol produced the maximum catalepsy at 90 min 212.66 ±10.23. In animals treated with MAE at dose of 100 mg/kg, 200 mg/kg and 400 mg/kg significantly potentiated haloperidol induced catalepsy at each time interval, in a dose dependent manner. At dose 100, 200 and 400 mg/kg, animals treated with MAE showed maximum cataleptic score of 228.33±12.29, 265.66±7.33 and 274.16±8.86 respectively at 120 min (p<0.001).Conclusions: Results indicate that the MAE have anti-psychotic effects in haloperidol induced catalepsy model in rats.

Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Delirium in the Critically Ill Patients: Is It Easily Diagnosed? What is the Incidence and What is the Management?

Introduction: Delirium is common in critically sick patients and related prolonged length of medical intensive care unit (ICU) and long-run psychological impairment. Aim of the study: The aim of the study is to assess the incidence of delirium in critically ill patients. Evaluate the effectiveness of diagnosing delirium by subjective global assessment compared to CAM-ICU score in critically ill patients. Evaluate the effect of haloperidol versus atypical antipsychotic drugs in the treatment. Methods: Total 200 critically ill patients selected sequentially on their admission to ICU and subjected for full medical history taking, clinical examination daily with emphasis on full neurological assessment, daily assessment of delirium along their stay in the ICU by 2 methods: subjective global assessment which is the subjective individual clinical impression performed by the attending resident in the ICU. CAM-ICU score which is performed by the physician in charge of the study using CAM-ICU worksheet. Results: Delirium is a frequent complication in the intensive care unit. The CAM-ICU scoring system appears to be rapid, valid, and reliable for diagnosing delirium in the ICU setting and may be a useful instrument for both clinical and research purposes. Use of objective criteria may identify patients mistakenly thought to have delirium who do not meet objective criteria for the diagnosis of the condition. The degree of agitation is an essential indicator of the dosage of the used antipsychotic drug, need for additional antipsychotics. Conclusion: Delirium is a common problem in critically ill patients and is not easy to manage.

Butea monosperma Reduces Haloperidol and Sulpiride Induced Hyperprolactinemia.

Background: Prolonged administration of neurolepticdrugs cause disrupted D dopamine receptor which 2leads to increased prolactin level, causesgyanaecomastia. Presently, dopamine receptor agonistis the choice of treatment for hyperprolactinemia. Aimand Objectives: The study aims to determine the antihyperprolactinemic effect of methanolic extract ofButea monosperma (MEBM) against haloperidol(HPL) and sulpiride (SPD) induced hyperprolactinemiaand to correlate with its active constituents. Materialand Methods: To induce hyperprolactinemia HPL 5mg/kg for 16 continuous days and SPD 20 mg/kg for 28continuous days was administred. MEBM 200mg/kg/day and 400 mg/kg/day were administered for16 and 28 days respectively half an hour beforeadministration of HPL and SPD. The serum prolactin(PRL) level, dopamine (DA) level and antioxidantstatus in the rat brain, hematological parameters weremeasured and histological examination of the anteriorpituitary gland, adrenal gland and spleen were done. Inaddition, antioxidant enzymes like superoxidedismutase (SOD) and catalase (CAT) were alsoestimated. Results: MEBM decreases serum PRL leveland increased DA level in brain significantly. Further,MEBM also restored SOD and CATstatus significantly.The inflammatory markers induced by HPL and SPDwere suppressed by MEBM. Discussion: Neuronal DAinhibition by neuroleptic drugs decreases the release ofDAwhich leads to hyperprolactinemia. MEBM (butrin)may activate DA neurones to ameliorate hyperprolactinaemia. The dopaminergic, anti-oxidant andanti-inflammatory effect of MEBM may be attributed toits anti-hyperprolactinemic effect. Conclusion: Buteamonosperma possesses anti-hyperprolactinemic effectwhich may be attributed to its marker constituent likeButrin.