Butorphanol for Post-Operative Analgesia - A Comparative Clinical Study with Ketorolac

Introduction: Butorphanol, an opioid derivative has been shown to have, in addition to its analgesic properties, several other advantageous effects like antistressor, sedative and anti-shivering action. The efficacy and safety profile of ketorolac, yet another widely used post-operative analgesic is well documented. This study aims to compare the two analgesics. Aims and objectives: This study was conducted to compare the analgesic efficacy and other effects of butorphanol and ketorolac, administered intramuscularly, in post-operative patients who have undergone lower abdominal and pelvic surgeries. Materials and methods: 50 patients undergoing lower abdominal and pelvic surgeries under general or spinal anaesthesia were randomly divided into two Groups (25 each). At a particular level of post-operative pain, the patients Groups I and II were administered intramuscular ketorolac 30mg and butorphanol 2mg respectively. The analgesic effect was studied using Visual Analogue Scale (VAS) and the verbal category scale. Patients were monitored for the sedative action, respiratory status and other vital parameters for 300 minutes and for other adverse reactions over the next twelve hours. Observations: Butorphanol provided better analgesia within the first two hours of administration, while ketorolac was more effective at 4-5 hours. Better sedative action without any significant respiratory depressant effect was demonstrated with butorphanol. There were no clinically significant hemodynamic fluctuations or adverse reactions with butorphanol or ketorolac. Conclusions: Butorphanol provides better early analgesia as compared to ketorolac with a desirable and safe sedative effect in post-operative patients who have undergone lower abdominal and pelvic surgeries

Comparison of two ketamine/xylazine anesthesic protocols in pigs (Sus crofa domestica)

The pig (Sus scrofa domestica) is an animal used as an experimental model in surgical procedures. This makes the use of anaesthesia necessary. The present study constitutes a comparison between two different ketamine/xylazine concentration protocols. One protocol used ketamine 10% + xylazine 10% (high concentration), and the other ketamine 5% + xylazine 2% (low concentration). Concentrations were chosen since these are the most common presentations in the veterinary market. In the present experiments, twenty male and female pigs (Sus crofa domestica; 20 kg each), were assigned into two different groups. The first one was integrated by pigs treated with high concentration protocol (n = 10), and the second one, composed by pigs that received low concentration protocol (n = 10). Parameters measured were the time in which the animals were placed in sternal decubitus, and the heart rate. The effects of these drugs were considered not only specifically in its sedative effects, but also in the respiratory system. Based on these results, we conclude that the first protocol showed better results than the second one. The time in which the animals were placed in sternal decubitus was lower in the first one (p < 0.001). Differences between the effects on the respiratory system (p = 0.37) and sedative effects (p = 0.87) were not significant, even when focusing on the last measurement, higher concentration protocol was twenty percent (20%) more effective than lower.Fil: Guevara, Manuel Alejandro. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lorenzo Aquaro, Sofía Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Giai, Marcos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gargiulo, Pascual Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Fundación Corporación Tecnológica Latinoamericana; Argentin

Uji Efek Sedatif Infusa Daun Kratom (Mitragyna Speciosa) Pada Mencit Jantan Galur Balb/c

Insomnia is a condition difficult start to sleep, can not sleep or inadequate sleepduration. One of plants which guess have sedative effect is kratom (Mitragyna speciosa). Thisresearch was conducted to determine the sedative effect of kratom leaves infusa to male BALB/cstrain mice. In addition, it aims to determine the effective dose and potential kratom leaves infusawhen compared with diazepamThe mice divided into 5 groups of positive control group (diazepam), negative control(aquadest), and infusa of kratom leaves groups dose 1,95; 3,9; and 7,8 g/KgBW. The test of sedativeeffect was conducted with Traction test and Fireplace test method on male BALB/c strain mice.Monitoring of quantitative data are duration time of mice to turning the body and duration time ofmice to fall down, as soon as duration time of mice to come out from cylinder tube. Qualitative data isobserved presence or absence of reflexes behind the body and corneal reflexes.Result of the quantitative data was analyzed with One Way ANOVA and supported by SPSS.Based on the result, all of kratom leaves infusa dosages has sedative effect, which is the mosteffective dose kratom leaves infusa at dose of 7.80 g / KgBW. But the sedative effect still below ofdiazepam

The Comparison of Gabapentin and Amitriptilin Effectivity as Pain Therapy in Herniated Nucleus Pulposus

Herniated nucleus pulposus (HNP) is one of peripheral neuropathic pain. Although concensus guidelines for the treatment of neuropathic pain are based on the results of the RCT studies, there are still gaps in the literatures. This study aimed to compare the effectiveness and quality of life of gabapentin and amitriptyline for the treatment of pain in HNP. The method used a quasi experimental with consequtive sampling. This study included 30 patients in the gabapentin group and 26 patients in the amitriptyline group, and each group was evaluated for 1 month. Effectiveness was assessed using Visual Analogue Scale (VAS) every 2 weeks then analized by independent and paired sample t test. The results showed that the use of gabapentin and amitriptilin in 4 weeks showed the decrease of pain score measured by visual analog scale 3.70 ± 0.349 and 3.500 ± 0.34 although there was no statistical difference (p value = 0.704). To sum up, effectiveness of gabapentin and amitriptyline in the treatment of neuropathic pain did not have statistical difference

High-throughput screening in larval zebrafish identifies novel potent sedative-hypnotics

BACKGROUND: Many general anesthetics were discovered empirically, but primary screens to find new sedative-hypnotics in drug libraries have not used animals, limiting the types of drugs discovered. The authors hypothesized that a sedative-hypnotic screening approach using zebrafish larvae responses to sensory stimuli would perform comparably to standard assays, and efficiently identify new active compounds. METHODS: The authors developed a binary outcome photomotor response assay for zebrafish larvae using a computerized system that tracked individual motions of up to 96 animals simultaneously. The assay was validated against tadpole loss of righting reflexes, using sedative-hypnotics of widely varying potencies that affect various molecular targets. A total of 374 representative compounds from a larger library were screened in zebrafish larvae for hypnotic activity at 10 µM. Molecular mechanisms of hits were explored in anesthetic-sensitive ion channels using electrophysiology, or in zebrafish using a specific reversal agent. RESULTS: Zebrafish larvae assays required far less drug, time, and effort than tadpoles. In validation experiments, zebrafish and tadpole screening for hypnotic activity agreed 100% (n = 11; P = 0.002), and potencies were very similar (Pearson correlation, r > 0.999). Two reversible and potent sedative-hypnotics were discovered in the library subset. CMLD003237 (EC50, ~11 µM) weakly modulated γ-aminobutyric acid type A receptors and inhibited neuronal nicotinic receptors. CMLD006025 (EC50, ~13 µM) inhibited both N-methyl-D-aspartate and neuronal nicotinic receptors. CONCLUSIONS: Photomotor response assays in zebrafish larvae are a mechanism-independent platform for high-throughput screening to identify novel sedative-hypnotics. The variety of chemotypes producing hypnosis is likely much larger than currently known.This work was supported by grants from Shanghai Jiaotong University School of Medicine, Shanghai, China, and the Chinese Medical Association, Beijing, China (both to Dr. Yang). The Department of Anesthesia, Critical Care and Pain Medicine of Massachusetts General Hospital, Boston, Massachusetts, supported this work through a Research Scholars Award and an Innovation Grant (both to Dr. Forman). Contributions to this research from the Boston University Center for Molecular Discovery, Boston, Massachusetts (to Drs. Porco, Brown, Schaus, and Xu, and to Mr. Trilles), were supported by a grant from the National Institutes of Health, Bethesda, Maryland (grant No. R24 GM111625). (Shanghai Jiaotong University School of Medicine, Shanghai, China; Chinese Medical Association, Beijing, China; Department of Anesthesia, Critical Care and Pain Medicine of Massachusetts General Hospital, Boston, Massachusetts; R24 GM111625 - National Institutes of Health, Bethesda, Maryland)Accepted manuscript2019-09-0

A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors

Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinkingFil: Bocarsly, Miriam E.. National Institutes of Health; Estados UnidosFil: da Silva e Silva, Daniel. National Institutes of Health; Estados UnidosFil: Kolb, Vanessa. National Institutes of Health; Estados UnidosFil: Luderman, Kathryn D.. National Institutes of Health; Estados UnidosFil: Shashikiran, Sannidhi. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sibley, David R.. National Institutes of Health; Estados UnidosFil: Dobbs, Lauren K.. National Institutes of Health; Estados Unidos. University of Texas at Austin; Estados UnidosFil: Álvarez, Verónica Alicia. National Institutes of Health; Estados Unido

Symptomatic treatment of children with anti-NMDAR encephalitis.

Abstract AIM: We performed the first study on the perceived benefit and adverse effects of symptomatic management in children with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHOD: A retrospective chart review was undertaken at two tertiary paediatric hospitals in Australia and New Zealand. We included 27 children (12 males, 15 females; mean age at admission 7y 1mo) with anti-NMDAR antibodies in serum or cerebrospinal fluid with a typical clinical syndrome. RESULTS: Only two out of 27 patients were white, whereas 16 out of 27 patients were from the Pacific Islands/New Zealand Maori. The mean duration of admission was 69 days (10-224d) and 48% of patients (13/27) needed treatment in an intensive care setting. A mean of eight medications per patient was used for symptomatic management. Symptoms treated were agitation (n=25), seizures (n=24), movement disorders (n=23), sleep disruption (n=17), psychiatric symptoms (n=10), and dysautonomia (n=four). The medications used included five different benzodiazepines (n=25), seven anticonvulsants (n=25), eight sedatives and sleep medications (n=23), five antipsychotics (n=12), and five medications for movement disorders (n=10). Sedative and sleep medications other than benzodiazepines were the most effective, with a mean benefit of 67.4% per medication and a mean adverse effect-benefit ratio of 0.04 per medication. Antipsychotic drugs were used for a short duration (median 9d), and had the poorest mean benefit per medication of 35.4% and an adverse effect-benefit ratio of 2.0 per medication. INTERPRETATION: Long-acting benzodiazepines, anticonvulsants, and clonidine can treat multiple symptoms. Patients with anti-NMDAR encephalitis appear vulnerable to antipsychotic-related adverse effects. Pacific Islanders appear to have a vulnerability to anti-NMDAR encephalitis in our region

Manual control analysis of drug effects on driving performance

The effects of secobarbital, diazepam, alcohol, and marihuana on car-driver transfer functions obtained using a driving simulator were studied. The first three substances, all CNS depressants, reduced gain, crossover frequency, and coherence which resulted in poorer tracking performance. Marihuana also impaired tracking performance but the only effect on the transfer function parameters was to reduce coherence

Sedative-like effect of intraperitoneal GABA administration in the open field test

Gamma-Amino Butyric Acid (GABA) is the main inhibitor neurotransmitter of the Central Nervous System (CNS). Its peripheral administration has been matter of discussion. On the one hand, it has been reported that it does not cross the Blood-Brain Barrier (BBB), and, on the other hand, it has been associated with multiple therapeutic regimens and supplements by peripheral administration. The aim of the present study is to elucidate the possibility of a central sedative effect when administered peripherally. An experimental cohort of 90-day-old Holtzman male rats weighing 240-270 g was used. It was divided into 2 groups: saline-controls (n = 9) and GABA treated rats (12.5 mg/kg, n = 9). Both groups were intraperitoneally injected. The motor behavioral patterns displayed in the Opto Varimex (OVM) were studied. Vertical, horizontal, ambulatory and non-ambulatory movements and the number of movements were recorded in an automated way. Horizontal movements constitute the integration of ambulatory and non-ambulatory movements. Student t test was used comparing groups. In this experiment, there were non-significant downward trends in vertical, ambulatory, non-ambulatory and number of movements. Ambulatory and non-ambulatory tendencies acquired significance when treated together as horizontal movements (p < 0.05). We may conclude that peripheral administration of GABA produced a decrease of the horizontal movements in the open field test. It may be interpreted as a sedative effect, suggesting a passage of GABA through BBB, with central effects. However, there are several alternative possibilities to explain present findings. Other experiments will elucidate the implications or scope of the present findings.Fil: Gargiulo, Augusto Pascual Ítalo. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Marquez Herrero, Santiago. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Romanowicz, Esteban Alejandro. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Guevara, Manuel Alejandro. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Landa, Adriana Inés. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Lafuente, José Vicente. Universidad del País Vasco; EspañaFil: Mesones, Humberto Luis. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Fundación Instituto de Neurobiología; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Gargiulo, Pascual Angel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentin

Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice

The severity and complexity of depression can vary widely among individuals, thus making single drug therapy ineffective in some cases. Taking this fact into account and using a mouse model, we set on investigating the possibility of obtaining a synergism of action between a classical tricyclic antidepressant that inhibits noradrenalin and serotonin reuptake (doxepin), and a modern antidepressant that inhibits type-B monoamine oxidase (selegiline). We measured the antidepressant effect using the forced swimming test and the tail suspension test. We determined motor activity using the Activity Cage test. Our results have shown that the antidepressant effect intensifies significantly in the animals treated with both antidepressants simultaneously compared to those treated only with doxepin. Furthermore, we observed that selegiline decreases the sedative effect of doxepin in the Activity Cage test