Determination of amfepramone hydrochloride, fenproporex, and diazepam in so-called natural capsules used in the treatment of obesity

A simple and rapid method was developed for the determination of amfepramone hydrochloride, fenprorex, and diazepam in capsules using high performance liquid chromatography (HPLC) with UV detection. This procedure provided conditions for the separation of the active ingredient from the complex matrices of the dosage forms by extraction in methanol. Isocratic reversed phase chromatography was performed using acetonitrile, methanol, and aqueous 0,1% ammonium carbonate (50:10:40) as a mobile phase, LiChrospher 100 RP 18 column (125 x 5 mm id, 5 mu m), a column temperature of 25 +/- 1 degrees C and detection at 230 nm.The calibration curves were linear over a wide concentration range (20-2000 mu g.mL(-1) to amfepramone hydrochloride, 8-800 mu g.mL(-1) to fenproporex, and 4-200 mu g.mL(-1) to diazepam) and good analytical recovery (87.1 to 107.8%) was obtained. The method is accurate and precise, as well as having advantages such as simplicity and short duration of analysis. Twenty samples of pharmaceutical preparations labelled as natural products were analysed. Anorectics and diazepam, were detected in 40% of the samples.

High-performance liquid chromatographic determination of amfepramone hydrochloride, mazindol, and diazepam in tablets

Simple and rapid procedures were developed for the quantification of amfepramone hydrochloride and diazepam and mazindol and diazepam in tablets using high performance liquid chromatography (HPLC) with UV detection. These techniques provided conditions for the separation of each active ingredient from the complex matrices of the dosage forms by dilution or extraction in methanol. Isocratic reversed phase chromatography was performed using acetonitrile, methanol, and aqueous 0,1% ammonium carbonate (70:10:20, v/v/v) as a mobile phase, Radial-Pak C-18 column (100 x 8 mm id, 4 mu m), a column temperature of 25+/-1 degrees C and detection at 255 nm. The calibration curves were linear over a wide concentration range (100-1000 mu g.mL(-1) to amfepramone hydrochloride and mazindol and 10-100 mu g.mL(-1) to diazepam) with good correlation factors of 0.9978, 0.9956 and 0.9997 for amfepramone hydrochloride, mazindol, and diazepam, respectively.Mean recoveries obtained from the two kinds of samples ranged from 83.2 to 102.5%, with coefficients of variation ranging from 1.0 to 6.1.These results demonstrated the efficiency of the proposed methods, as well as advantages such as simplicity and short duration of analysis.

Influência do ciclo estral no efeito do diazepam na ansiedade e memória de ratas

Memory and anxiety are related phenomena. Several evidences suggest that anxiety is fundamental for learnining and may facilitate or impair the memory formation process depending of the context. The majority of animal studies of anxiety and fear use only males as experimental subjects, while studies with females are rare in the literature. However, the prevalence in phobic and anxiety disorders is greater in women than in men. Moreover, it is known that gender maybe influence benzodiazepine effects, the classic drugs used for anxiety disorders treatment. In this respect, to further investigate if fear/anxiety aspects related to learning in female subjects would contribute to the study of phobic and anxiety disorders and their relationship with learning/memory processes, the present work investigates (a) the effects of benzodiazepine diazepam on female rats performance in a aversive memory task that assess concomitantly anxiety/emotionality, as the interaction between both; (b) the influence of estrous cycle phases of female rats on diazepam effects at aversive memory and anxiety/emotionality, and the interaction between both and (c) the role of hormonal fluctuations during estrous cycle phases in absence of diazepam effects in proestrus, because female rats in this phase received or not mifepristone, the antagonist of progesterone receptor, previously to the diazepam treatment. For this purpose, the plus maze discriminative avoidance task, previously validated for studies of anxiety concomitantly to learning/memory, was used. The apparatus employed is an adaptation of a conventional plus maze, with two opens arms and two closed arms, one of which presenting aversive stimulation (noise and light). The parameters used were: time in non-aversive arm compared to time in aversive and percentage of time in aversive arm on several temporal divisions, in order to evaluate memory; percentage of time in open arms, risk assessment, head dipping and end exploring to evaluate anxiety ; and distance traveled for locomotion. In experiment I, we found anxiolytic effect of diazepam only for 4 mg/kg dose, however the amnestic effect appear at a dose of 2 mg/kg. In second experiment, rats were divided in groups according estrous cycle phase (metaestrus/diestrus, proestrus e estrus). In this experiment, when we considered estrous cycle phase or diazepam treatment, the results did not demonstrate any differences in anxiety/emotionality parameters. The amnestic effects of diazepam occur in female rats in metestrus/diestrus and estrus and is absent in proestrous rats. Proestrous female rats that received mifepristone exhibited the amnestic effect of diazepam and also anxiolytic effects, that it was not previously observed in this dose. The results have demonstrated dissociation of anxiolytic and amnestic diazepam effects, not previously observed in males; the absence of amnestic effect of diazepam in proestrous phase; and the possible role of progesterone in aversive memory over diazepam effect, because the mifepristone, associated with diazepam, caused amnestic effect in proestrus

Avaliação dos efeitos do biperideno, diazepam e neuropeptídeos S sobre a memória e a ansiedade na tarefa do labirinto em T elevado em camundongos

Anxiety is an emotional phenomenon, and normally it is interpreted as an adaptative behavior front to adversities. In its pathological form, anxiety can severely affect aspects related to the personal and professional life. Studies have shown a close relationship between anxiety disorders and aversive memory processing. Considering that the pharmacotherapy of anxiety disorders is still limited, innovative anxiolytic agents are needed. In this regard, neuropeptides systems are interesting therapeutic targets to the treatment of psychopathologies. Neuropeptide S (NPS), a 20-aminoacid peptide, is the endogenous ligand of a G-protein coupled receptor (NPSR), which has been reported to evoke hyperlocomotion, awakefull states, besides anxiolysis and memory improvements in rodents. This study aimed to investigate the effects of biperiden (BPR; an amnesic drug), diazepam (DZP; an anxiolytic drug) and NPS at three distinct times: pre-training, post-training, and pre-test, in order to assess anxiety and memory process in the same animal model. The elevated Tmaze (ETM) is an apparatus derived from the elevated plus-maze test, which consists of one enclosed and two open arms. The procedure is based on the avoidance of open spaces learned during training session, in which mice were exposed to the enclosed arm as many times as needed to stay 300 s. In the test session, memory is assessed by re-exposing the mouse to the enclosed arm and the latency to enter an open arm was recorded. When injected pre-training, BPR (1 mg/kg) impaired learning and memory processing; DZP (1 and 2 mg/kg) evoked anxiolysis, but only at the dose of 2 mg/kg impaired memory; and NPS 0.1 nmol induced anxiolysis without affecting memory. Post-training injection of DZP (2 mg/kg) or BPR (1 and 3 mg/kg) did not affect memory consolidation, while the post-trainning administration of NPS 1 nmol, but not 0.1 nmol, improved memory in mice. Indeed, pre-trainning administration of NPS 1 nmol did not prevent memory impairment elicited by BPR (2 mg/kg, injected before training). In the open field test, BPR 1 mg/kg and NPS 1 nmol induced hyperlocomotion in mice. In conclusion, the proposed ETM task is practical for the detection of the anxiolytic and amnesic effects of drugs. The anxiolytic and memory enhancement effects of NPS were detected in the ETM task, and reinforce the role of NPS system as an interesting therapeutic target to the treatment of anxiety disorders

Parametria da associação do midazolam ou diazepam em cães pré-tratados pela atropina e tratados pela dexmedetomidina e quetamina

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Zero valent iron mediated degradation of the pharmaceutical diazepam

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Photodegradation of lincomycin and diazepam in sewage treatment plant effluent by photo-Fenton process

First, the effect of ferrioxalate or iron nitrate on the photo-Fenton degradation efficiency of the pharmaceuticals lincomycin (LCM) and diazepam (DZP) was evaluated. The degradation of both pharmaceuticals was improved in the presence of ferrioxalate in relation to Fe(NO(3)), either under black-light or solar irradiation. The degradation of the pharmaceuticals was then evaluated when present in an effluent from sewage treatment plant (STP) under black-light irradiation. Pharmaceuticals oxidation was not influenced by the matrix, since very similar results were obtained when compared to the experiments carried out in distilled water. However, DOC removal was slightly affected by the matrix, due probably to the generation of recalcitrant intermediates during effluent photodegradation and to the high content of inorganic carbon of STP effluent. Even so, high DOC removal percentages were achieved, 65% for lincomycin and 80% for diazepam after 60 min irradiation. (C) 2010 Elsevier B.V. All rights reserved.

Effects of diethylpropion treatment and withdrawal on aorta reactivity, endothelial factors and rat behavior

Diethylpropion (DEP) is an amphetamine-like compound used as a coadjutant in the treatment of obesity and which presents toxicological importance as a drug of abuse. This drug causes important behavioral and cardiovascular complications; however, the vascular and behavioral alterations during DEP treatment and withdrawal, have not been determined. We evaluated the effects of DEP treatment and withdrawal on the rat aorta reactivity to noradrenaline, focusing on the endothelium, and the rat behavior during DEP treatment and withdrawal. DEP treatment caused a hyporreactivity to noradrenaline in aorta, reversible after 2 days of withdrawal and abolished by both the endothelium removal and the presence of L-NAME, but not by the presence of indomethacin. Furthermore, DEP treatment increased the general activity of rats. Contrarily, DEP withdrawal caused a decrease in the locomotor activity and an increase in grooming behavior, on the 2nd and 7th days after the interruption of the treatment, respectively. DEP treatment also caused an adaptive vascular response to noradrenaline that seems to be dependent on the increase in the endothelial nitric oxide system activity, but independent of prostaglandins synthesis. The data evidenced chronological differences in the adaptive responses of the vascular and central nervous systems induced by DEP treatment. Finally, a reversion of the adaptive response to DEP was observed in the vascular system during withdrawal, whereas a neuroadaptive process was still present in the central nervous system post-DEP. These findings advance on the understanding of the vascular and behavioral pathophysiological processes involved in the therapeutic and abusive uses of DEP. (C) 2003 Elsevier B.V. (USA). All rights reserved.

EFFECTS OF FENCAMFAMINE WITHDRAWAL IN RATS

1. The effects produced by discontinuation of long-term treatment with fencamfamine (FCF) were evaluated recording behavioral and body weight changes.2. 48 hr after withdrawal of FCF rats shelved a significant decrease in exploratory behavior when compared to saline-treated ones.3. Discontinuation of treatment with FCF resulted in a significant increase in body weight on days of drug withdrawal.4. These results suggest that FCF caused signs of withdrawal similar to other psychostimulant drugs.

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50).Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.Funding Bristol-Myers Squibb.

Avaliação paramétrica do cloridrato de dexmedetomidina em cães pré-tratados pela atropina e tratados pela quetamina em associção com o midazolam e/ou diazepam

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação neurocomportamental de ratos expostos agudamente ao fipronil: influência de diazepam e flumazenil

Pós-graduação em Medicina Veterinária - FMVZ

The effects of diazepam on the elevated T-maze are dependent on the estrous cycle of rats

In order to determine the modulation of anxiolytic and panicolytic-like effects of diazepam by the hormonal cycle of female rats, male and female rats – the latter divided per estrous cycle phase (estrus, diestrus, metaestrus and proestrus) – were tested in the elevated T-maze, a behavioral model of panic and anxiety. Diazepam (0.5, 1.0 and 2.0 mg/kg) or saline solution was injected in individual animals that were submitted to one session in the elevated T-maze 25 min after drug/saline administration. The test consisted of three avoidance trials and one escape trial, separated by a 30 s interval, during which the animals were isolated in individual cages. The avoidance trials began with the animal being placed at the end of the maze's enclosed arm. The time necessary for the animal to leave the central square was considered as the response's latency. The trials that exceeded 300 s were considered as failures. Results demonstrate a decrease in the effects of diazepam in inhibitory avoidance (anxiety) trials in females in diestrus and proestrus, but no relation of gender or estrous cycle on diazepam effects on escape trials (fear). The results support the hypothesis that down-regulation of GABAA receptors by activation of nuclear estrogen receptors and induction of PKC-mediated GABAA receptor phosphorylation by activation of surface estrogen receptors in raphe neurons underlie the modulation of diazepam sensitivity by estrogen.