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Marcos N. Eberlin - One of the best experts on this subject based on the ideXlab platform.
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Quantitation of drugs via molecularly imprinted polymer solid phase extraction and electrospray ionization mass spectrometry: benzodiazepines in human plasma
Inglaterra, 2015Co-Authors: Ec Figueiredo, Gustavo B. Sanvido, Sparrapan R, Mg Santos, Arruda Maz, Marcos N. EberlinAbstract:Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The association of solid phase extraction with molecularly imprinted polymers (MIP) and electrospray ionization mass spectrometry (ESI-MS) is applied to the direct extraction and quantitation of benzodiazepines in human plasma. The target analytes are sequestered by MIP and directly analyzed by ESI-MS. Due to the MIP highly selective extraction, ionic suppression during ESI is minimized; hence no separation is necessary prior to ESI-MS, which greatly increases analytical speed. Benzodiazepines (medazepam, nitrazepam, diazepam, Chlordiazepoxide, clonazepam and midazolam) in human plasma were chosen as a proof-of-principle case of drug analyses by MIP-ESI-MS in a complex matrix. MIP-ESI-MS displayed good figures of merits for medazepam, nitrazepam, diazepam, Chlordiazepoxide and midazolam, with analytical calibration curves ranging from 10 to 250 mu g L(-1) (r > 0.98) with limit of quantification
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Quantitation of drugs via molecularly imprinted polymer solid phase extraction and electrospray ionization mass spectrometry: benzodiazepines in human plasma.
Analyst, 2011Co-Authors: Eduardo Costa Figueiredo, Regina Sparrapan, Gustavo B. Sanvido, Mariane Gonçalves Santos, Marco Aurélio Zezzi Arruda, Marcos N. EberlinAbstract:The association of solid phase extraction with molecularly imprinted polymers (MIP) and electrospray ionization mass spectrometry (ESI-MS) is applied to the direct extraction and quantitation of benzodiazepines in human plasma. The target analytes are sequestered by MIP and directly analyzed by ESI-MS. Due to the MIP highly selective extraction, ionic suppression during ESI is minimized; hence no separation is necessary prior to ESI-MS, which greatly increases analytical speed. Benzodiazepines (medazepam, nitrazepam, diazepam, Chlordiazepoxide, clonazepam and midazolam) in human plasma were chosen as a proof-of-principle case of drug analyses by MIP-ESI-MS in a complex matrix. MIP-ESI-MS displayed good figures of merits for medazepam, nitrazepam, diazepam, Chlordiazepoxide and midazolam, with analytical calibration curves ranging from 10 to 250 μg L−1 (r > 0.98) with limit of quantification
Roberto Frussafilho - One of the best experts on this subject based on the ideXlab platform.
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role of learning of open arm avoidance in the phenomenon of one trial tolerance to the anxiolytic effect of Chlordiazepoxide in mice
Life Sciences, 2005Co-Authors: Mariana Bendlin Calzavara, Regina H Silva, Camilla L Patti, G B Lopez, Vanessa C Abilio, Roberto FrussafilhoAbstract:A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic efficacy of benzodiazepines on a second trial. Some possible explanations to the occurrence of this phenomenon (one-trial tolerance-OTT) involve behavioral modifications thought to be consequence of some kind of learning in the first trial. In the present study, the influence of learning-impairing situations on the effects of the benzodiazepine Chlordiazepoxide on mice re-tested in the EPM is investigated. The results showed that: (1) as expected, the administration of Chlordiazepoxide to mice re-tested in the EPM- under the same conditions of the first trial- failed to induce anxiolysis; (2) a decreased percent time in the open arms was observed on the second trial of mice exposed to both trials under the same experimental conditions; (3) neither the increase in open arm avoidance by mice re-exposed to the EPM nor the OTT to Chlordiazepoxide effect were modified by administration of the amnestic agent scopolamine; (4) the decrement of the duration of the first trial to 1 min or the change in light and noise conditions in both trials counteracted the increase in open arm avoidance on trial 2; (5) none of the later procedures modified the phenomenon of OTT. Although not discarding the modulation exerted by other memory processes in the OTT phenomenon, the results indicate that situations that impair the learned avoidance response to the open arms in the EPM do not modify the phenomenon of OTT.
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one trial tolerance to the effects of Chlordiazepoxide in the elevated plus maze is not due to acquisition of a phobic avoidance of open arms during initial exposure
Life Sciences, 2002Co-Authors: Roberto Frussafilho, R De A RibeiroAbstract:A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic-like efficacy of benzodiazepines. This phenomenon called one-trial tolerance has been suggested to represent the acquisition of a phobic-like response to the open arms during trial 1. The present study was designed to examine the effects of Chlordiazepoxide (5 mg/kg, ip) on the behaviour of rats in a conventional EPM apparatus after previous exposure to a four-open-arm EPM, a four-enclosed arm EPM or a conventional EPM, as well as in naive rats. Chlordiazepoxide had clear-cut anxiolytic-like effects (increased percentage of time spent on the open arms) in a traditional EPM in naive rats and in animals previously exposed to a four-open-arm EPM. However, it was ineffective in rats previously exposed to a traditional or a four-closed-arm EPM. Thus, the phenomenon of one-trial tolerance does not depend upon initial open-arm experience.
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the plus maze discriminative avoidance task a new model to study memory anxiety interactions effects of Chlordiazepoxide and caffeine
Journal of Neuroscience Methods, 2000Co-Authors: Regina H Silva, Roberto FrussafilhoAbstract:The plus-maze discriminative avoidance paradigm is a new animal model of learning/memory that provides simultaneous information about anxiety. Mice are conditioned to choose between the two enclosed arms (in one of which light and noise are presented as aversive stimuli) while avoiding the two open arms of the apparatus. The test has the advantage of measuring, at the same time and in the same animals, learning/memory (by the percent time spent in aversive enclosed arm — PTAV) and anxiety (by the percent time spent in the open arms — PTO). The effects of Chlordiazepoxide and caffeine on learning/memory and anxiety of mice tested in this paradigm were investigated. Chlordiazepoxide (5 mg/kg) significantly increased and caffeine (20 mg/kg) significantly decreased PTO during the training session, suggesting an anxiolytic and an anxiogenic effect, respectively. In the test session, Chlordiazepoxide- or caffeine-treated mice presented higher PTAV, suggesting amnestic effects. Given together, Chlordiazepoxide plus caffeine did not alter PTO, and the amnesic effect produced by each drug was no longer observed. It is concluded that learning/memory depends on an optimum emotional level. The plus-maze discriminative avoidance model appears to be a useful test to investigate this critical relationship between learning/memory and anxiety.
R Shruthi - One of the best experts on this subject based on the ideXlab platform.
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a randomized open label standard controlled parallel group study of efficacy and safety of baclofen and Chlordiazepoxide in uncomplicated alcohol withdrawal syndrome
Biomedical journal, 2016Co-Authors: K Girish, Vikram K Reddy, Lakshmi V Pandit, H P Pundarikaksha, R Vijendra, K Vasundara, R Manjunatha, Moulya Nagraj, R ShruthiAbstract:Background Alcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of Chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with Chlordiazepoxide in uncomplicated AWS.
Godwin O. Emerole - One of the best experts on this subject based on the ideXlab platform.
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hepatic drug metabolizing enzyme induction and serum triacylglycerol elevation in rats treated with Chlordiazepoxide griseofulvin rifampicin and phenytoin
Clinica Chimica Acta, 1999Co-Authors: Olatunde E Farombi, Oluyemi Akinloye, Clement O Akinmoladun, Godwin O. EmeroleAbstract:Abstract Five days intraperitoneal administration of rats with Chlordiazepoxide (0.4 mg/kg), griseofulvin (7 mg/kg), rifampicin (8.6 mg/kg), phenytoin (4.3 mg/kg) and phenobarbitone (1.4 mg/kg; an established inducer of microsomal enzymes) caused a significant increase in serum triacylglycerol ( P N -demethylase and p -nitroanisole O -demethylase ( P N -demethylase and p -nitroanisole O -demethylase activities were increased 1.48-, 1.15- and 1.47-fold, respectively, in Chlordiazepoxide-treated rats, 1.65-, 1.20- and 1.38-fold in griseofulvin-treated rats, 1.74-, 1.36- and 1.44-fold in rifampicin-treated rats, 1.56-, 1.29- and 1.62-fold in phenytoin-treated rats and 2.26-, 1.72- and 1.93-fold in phenobarbitone-treated rats. Chlordiazepoxide, griseofulvin, rifampicin, phenytoin and phenobarbitone increased the activity of cytosolic phosphatidate phosphohydrolase by 52, 58, 67, 73 and 82%, respectively, while the drugs elicited 50, 60, 60, 73 and 87% increases in the activity of the microsomal phosphatidate phosphohydrolase. Similarly, Chlordiazepoxide, griseofulvin, rifampicin, phenytoin and phenobarbitone elicited 2.4-, 2.39-, 2.34-, 1.69- and 3.75-fold increases in serum triacylglycerol concentrations. The correlations between serum triacylglycerol concentrations and the activities of aniline hydroxylase, aminopyrine N -demethylase and p -nitroanisole O -demethylase were significant in all treatment groups ( r =0.83, r =0.92 and r =0.87, respectively, n =30, P
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hepatic drug metabolizing enzyme induction and serum triacylglycerol elevation in rats treated with Chlordiazepoxide griseofulvin rifampicin and phenytoin
Clinica Chimica Acta, 1999Co-Authors: Olatunde E Farombi, Oluyemi Akinloye, Clement O Akinmoladun, Godwin O. EmeroleAbstract:Five days intraperitoneal administration of rats with Chlordiazepoxide (0.4 mg/kg), griseofulvin (7 mg/kg), rifampicin (8. 6 mg/kg), phenytoin (4.3 mg/kg) and phenobarbitone (1.4 mg/kg; an established inducer of microsomal enzymes) caused a significant increase in serum triacylglycerol (P<0.001) and the activities of aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase (P<0.001). Aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase activities were increased 1.48-, 1.15- and 1.47-fold, respectively, in Chlordiazepoxide-treated rats, 1.65-, 1.20- and 1.38-fold in griseofulvin-treated rats, 1.74-, 1.36- and 1.44-fold in rifampicin-treated rats, 1.56-, 1.29- and 1.62-fold in phenytoin-treated rats and 2.26-, 1.72- and 1.93-fold in phenobarbitone-treated rats. Chlordiazepoxide, griseofulvin, rifampicin, phenytoin and phenobarbitone increased the activity of cytosolic phosphatidate phosphohydrolase by 52, 58, 67, 73 and 82%, respectively, while the drugs elicited 50, 60, 60, 73 and 87% increases in the activity of the microsomal phosphatidate phosphohydrolase. Similarly, Chlordiazepoxide, griseofulvin, rifampicin, phenytoin and phenobarbitone elicited 2.4-, 2.39-, 2.34-, 1.69- and 3.75-fold increases in serum triacylglycerol concentrations. The correlations between serum triacylglycerol concentrations and the activities of aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase were significant in all treatment groups (r=0.83, r=0.92 and r=0.87, respectively, n=30, P<0.001). Our results suggest that induction of hepatic enzymes by the administered drugs may lead to hypertriglyceridaemia as an adverse effect, possibly by inducing the activity of regulatory enzymes in the biosynthesis of triglyceride.
Raymond M Quock - One of the best experts on this subject based on the ideXlab platform.
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Antagonism by NOS Inhibition of the Behavioral Effects of Benzodiazepine and GABA_A Receptor Agonists in the Mouse Elevated Plus-Maze
Neuropsychopharmacology, 2004Co-Authors: Geraldine S Elfline, Emily M Branda, Michael Babich, Raymond M QuockAbstract:Earlier we implicated nitric oxide (NO) in mediation of the behavioral effects of benzodiazepines. Since benzodiazepines work through facilitation of GABAergic inhibitory neurotransmission, this study was designed to determine whether the direct-acting γ -aminobutyric acid_A (GABA_A) receptor agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) evokes behavioral effects similar to those of benzodiazepines and whether behavioral effects of THIP are also NO dependent. When challenged with either Chlordiazepoxide or THIP in an elevated plus-maze paradigm, male NIH Swiss mice exhibited a dose-related increase in open-arm activity. The Chlordiazepoxide-induced effects were sensitive to antagonism by a benzodiazepine antagonist, and the effects of THIP were blocked by a GABA_A receptor antagonist. Pretreatment with the NO synthase (NOS) inhibitor L -N^G-nitro arginine antagonized the effects of both Chlordiazepoxide and THIP; similar pretreatment with the D -isomer, D -N^G-nitro arginine, which is inactive as an NOS inhibitor, was without effect on Chlordiazepoxide and THIP. These findings indicate that Chlordiazepoxide and THIP evoke similar behavioral effects in mice in the elevated plus-maze through actions on different parts of the GABA_A receptor, and that NO appears to play a key role in mediation of the behavioral effects of both Chlordiazepoxide and THIP.
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benzodiazepine receptor mediated behavioral effects of nitrous oxide in the rat social interaction test
Pharmacology Biochemistry and Behavior, 1993Co-Authors: Raymond M Quock, Pamela J Wetzel, Roger H Maillefer, Bradley L Hodges, Bradley A Curtis, Donald A CzechAbstract:The present study was conducted to ascertain whether an anxiolytic effect of nitrous oxide was demonstrable in rats using the social interaction test and whether this drug effect might be mediated by benzodiazepine receptors. Compared to behavior of vehicle-pretreated, room air-exposed rats, rat pairs exposed to nitrous oxide showed a generally inverted U-shaped dose-response curve with the maximum increase in social interaction encounters occurring at 25% and significant increase in time of active social interaction at 15-35%; higher concentrations produced a sedative effect that reduced social interaction. Treatment with 5.0 mg/kg of the anxiolytic benzodiazepine Chlordiazepoxide also increased social interaction. Pretreatment with 10 mg/kg of the benzodiazepine receptor blocker flumazenil, which alone had no effect, significantly antagonized the social interaction-increasing effects of both nitrous oxide and Chlordiazepoxide. In summary, these findings suggest that nitrous oxide produces a flumazenil-sensitive effect comparable to that of Chlordiazepoxide and implicate central benzodiazepine mechanisms in mediation of the anxiolytic effect of nitrous oxide.
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possible involvement of nitric oxide in Chlordiazepoxide induced anxiolysis in mice
Life Sciences, 1992Co-Authors: Raymond M Quock, Elizabeth NguyenAbstract:Mice challenged with the anxiolytic benzodiazepine Chlordiazepoxide exhibited significant increases in the percent of total entries into and percent of total time spent on open arms of an elevated plus maze. Systemic pretreatment with the nitric oxide synthase-inhibitor L-NG-nitro arginine (L-NOARG) antagonized these effects of Chlordiazepoxide. This inhibitory effect of L-NOARG was stereospecifically and completely reversed by intracerebroventricular administration of L-arginine but not D-arginine. These findings suggest a possible role of nitric oxide in the anxiolytic effect of Chlordiazepoxide in the elevated plus maze.