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1.
J Psychopharmacol ; 36(4): 470-478, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35485852

RESUMO

BACKGROUND: Benzodiazepines, Z-drugs, pregabalin, and melatonin (BZPMs) have been associated with a higher risk of traffic accidents, but the evidence is inconsistent, and lacking for newer drugs. AIM: To examine the association of BZPMs with risk of traffic accidents. METHODS: All Danish adults (n = 3,823,588) were followed for redeemed prescriptions of BZPM and for incident traffic accidents registered in Danish registers from 2002 through 2018. Associations were examined in cohort and case-crossover designs using Cox proportional hazard and conditional logistic regression with adjustment for co-variables. RESULTS: A total of 19.3% (n = 738,019) of all participants initiated treatment with BZPMs. During the mean follow-up of 10.3 years, 595,173(15.5%) of participants were involved in a traffic accident. In the cohort analysis, all BZPMs besides pregabalin were associated with a higher risk of traffic accidents in adults below 70 years, with chlordiazepoxide showing the strongest association (hazard ratio (HR)age 18-49 = 1.76, 95% confidence interval (CI): 1.67-1.86 and HRage 50-69 = 1.84, 95% CI: 1.70-2.00). In the older age groups, the specific BZPM medications were associated with lower or no risk of traffic accidents. However, in case-time-crossover analysis with inherited control for confounders, no BZPM medication was positively associated with traffic accidents, except for chlordiazepoxide, which had a higher odds ratio in middle-aged group (1.62, 95% CI: 1.15-2.29). CONCLUSIONS: This study does not fully support that BZPM use is a risk factor for traffic accidents. However, a positive association was found for chlordiazepoxide, which is approved for treatment of acute alcohol withdrawal.


Assuntos
Alcoolismo , Melatonina , Síndrome de Abstinência a Substâncias , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Benzodiazepinas/efeitos adversos , Clordiazepóxido , Estudos de Coortes , Estudos Cross-Over , Dinamarca/epidemiologia , Humanos , Melatonina/efeitos adversos , Pessoa de Meia-Idade , Pregabalina/efeitos adversos , Adulto Jovem
2.
J Exp Anal Behav ; 116(1): 3-20, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34144632

RESUMO

Extended pausing during discriminable transitions from rich-to-lean conditions can be viewed as escape (i.e., rich-to-lean transitions function aversively). Thus, an anxiolytic drug would be predicted to mitigate the aversiveness and decrease pausing. In the current experiment, pigeons' key pecking was maintained by a multiple fixed-ratio fixed-ratio schedule of rich (i.e., larger) or lean (i.e., smaller) reinforcers. Intermediate doses (3.0-10.0 mg/kg) of chlordiazepoxide differentially decreased median pauses during rich-to-lean transitions. Relatively small decreases in pauses occurred during lean-to-lean and rich-to-rich transitions. Effects of chlordiazepoxide on pausing occurred without appreciable effects on run rates. These findings suggest that signaled rich-to-lean transitions function aversively.


Assuntos
Condicionamento Operante , Reforço Psicológico , Animais , Clordiazepóxido/farmacologia , Columbidae , Esquema de Reforço
3.
Int. j. med. surg. sci. (Print) ; 8(1): 1-12, mar. 2021. tab
Artigo em Espanhol | LILACS | ID: biblio-1151620

RESUMO

El objetivo de este estudio fue caracterizar la prescripción de los medicamentos ansiolíticos utilizados en población de adultos mayores institucionalizados en el hogar de ancianos de Pinar del Río durante el año 2017.Se realizó un estudio descriptivo transversal, con recogida de datos retrospectiva, sobre prescripción de medicamentos ansiolíticos en la población de adultos mayores institucionalizados en el hogar de ancianos, se analizó la forma de utilización de los medicamentos, su indicación y prescripción con elementos de esquema terapéutico y factores que condicionan los hábitos de prescripción. Se trabajó con el universo (U= 98) de estudio el cual estuvo conformado por el total de pacientes institucionalizados, que estaban consumiendo ansiolíticos. Se revisaron las historias clínicas individuales y se confeccionó un modelo de recolección de datos.El medicamento más consumido por los adultos mayores fue el nitrazepam (41,8 %), siendo este a su vez el más consumido por el sexo masculino, no así para el femenino que resultó ser el clorodiazepóxido (64,6 %), el grupo de edad que más predominó fue el de 60-69 años, asimismo los viudos y el nivel educacional primario, el 79,5 % de los ancianos consume otros medicamentos que poseen interacción farmacocinética. El profesional que más indicó fue el médico de familia, la prescripción e intervalos entre dosis fue adecuada, la prescripción se consideró no racional.La prescripción de ansiolíticos en la población objeto de estudio, disminuye a medida que aumenta la edad, los más consumidores son los del sexo masculino y los institucionalizados por abandono familiar, esto apunta a la necesidad de continuar trabajando desde el nivel primario de atención dado que es de donde proceden estos ancianos.


The objective of this study was to characterize the prescription of anxiolytic medications used in the institutionalized elderly population at the Pinar del Río Nursing Home during 2017.A cross-sectional descriptive study was carried out, with retrospective data collection, on the prescription of anxiolytic medications in the population of institutionalized older adults in the Nursing Home, the form of use of the medications, their indication and prescription with elements of the therapeutic scheme was analyzed and factors that condition prescription habits. We worked with the universe (U = 98) of the study, which was made up of the total number of institutionalized patients who were consuming anxiolytics. Individual medical records were reviewed and a data collection model was created.The drug most consumed by older adults was nitrazepam (41.8%), this in turn being the most consumed by males, not so for females, which turned out to be chlorodiazepoxide (64.6%), the group The most prevalent age group was 60-69 years, likewise widowers and primary educational level, 79.5% of the elderly consume other drugs that have pharmacokinetic interaction. The professional who indicated the most was the family doctor, the prescription and intervals between doses were adequate, the prescription was considered non-rational.The prescription of anxiolytics in the population under study decreases as age increases, the most consumers are those of the male sex and those institutionalized due to family abandonment, this points to the need to continue working from the primary level of care since that is where these elders come from.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Prescrições de Medicamentos , Ansiolíticos/uso terapêutico , Clordiazepóxido/uso terapêutico , Instituição de Longa Permanência para Idosos , Nitrazepam/uso terapêutico , Casas de Saúde , Epidemiologia Descritiva , Estudos Transversais , Estudos Retrospectivos , Distribuição por Sexo , Distribuição por Idade
4.
BMJ Case Rep ; 14(1)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472809

RESUMO

Acute abdominal pain is a common presentation to the emergency department (ED). Ruling out life-threatening causes and giving pain relief are the most important tasks in ED. We describe a 32-year-old man who presented to ED with abdominal pain and vomiting which was unrelieved by usual doses of analgesic. Extensive investigations revealed no significant abnormalities. On further probing, he admitted taking traditional medications for infertility. The toxicological panel revealed a high blood lead level, leading to a diagnosis of acute lead toxicity. Chelation therapy with D-penicillamine was initiated and the patient's abdominal pain resolved within 4 days.


Assuntos
Dor Abdominal/diagnóstico , Medicamentos Falsificados/efeitos adversos , Intoxicação por Chumbo/diagnóstico , Charlatanismo , Vômito/diagnóstico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Doença Aguda , Adulto , Anemia/etiologia , Antieméticos/uso terapêutico , Quelantes/uso terapêutico , Clordiazepóxido/uso terapêutico , Antagonistas Colinérgicos , Constipação Intestinal/etiologia , Medicamentos Falsificados/química , Combinação de Medicamentos , Serviço Hospitalar de Emergência , Humanos , Intoxicação por Chumbo/complicações , Intoxicação por Chumbo/tratamento farmacológico , Masculino , Parassimpatolíticos/uso terapêutico , Penicilamina/uso terapêutico , Fenetilaminas/uso terapêutico , Quinuclidinas/uso terapêutico , Tomografia Computadorizada por Raios X , Vômito/tratamento farmacológico , Vômito/etiologia
6.
Psychosomatics ; 61(5): 544-550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32591212

Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Antipsicóticos/uso terapêutico , Infecções por Coronavirus/terapia , Delírio/tratamento farmacológico , Hipnóticos e Sedativos/efeitos adversos , Pneumonia Viral/terapia , Agitação Psicomotora/tratamento farmacológico , Medicamentos Indutores do Sono/uso terapêutico , Idoso , Analgésicos Opioides/efeitos adversos , Azepinas/uso terapêutico , Betacoronavirus , COVID-19 , Depressores do Sistema Nervoso Central/uso terapêutico , Clordiazepóxido/efeitos adversos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/psicologia , Delírio/etiologia , Delírio/fisiopatologia , Delírio/psicologia , Dexmedetomidina/efeitos adversos , Feminino , Guanfacina/uso terapêutico , Haloperidol/uso terapêutico , Humanos , Hidromorfona/efeitos adversos , Unidades de Terapia Intensiva , Ketamina/efeitos adversos , Melatonina/uso terapêutico , Midazolam/efeitos adversos , Oxicodona/efeitos adversos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Pneumonia Viral/psicologia , Propofol/efeitos adversos , Agitação Psicomotora/etiologia , Agitação Psicomotora/fisiopatologia , Agitação Psicomotora/psicologia , Respiração Artificial , SARS-CoV-2 , Transtornos do Sono do Ritmo Circadiano/tratamento farmacológico , Transtornos do Sono do Ritmo Circadiano/etiologia , Transtornos do Sono do Ritmo Circadiano/fisiopatologia , Traqueostomia , Triazóis/uso terapêutico , Ácido Valproico/uso terapêutico
7.
Behav Pharmacol ; 31(1): 73-80, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31625973

RESUMO

Linalool is an enanitomer monoterpene compound identified as the pharmacologically active constituent in a number of essential oils and has been reported to display anxiolytic properties in humans and in animal models and to exert both GABAergic and glutamatergic effects. In Experiment 1 linalool (100, 200, and 300, i.p.) had no significant effects compared with saline in an activity tracker with C57BL/6j mice. Experiment 2 assessed the effects on operant extinction with mice of chlordiazepoxide at a dose (15 mg/kg, i.p.) previously shown to facilitate extinction, and the same doses of linalool, compared with saline. Linalool had a dose-related facilitatory effect on extinction. While the effects of the highest dose of linalool most closely resembled the effects of chlordiazepoxide, the pattern of results suggested that linalool may affect both the acquisition of extinction learning, which is influenced by glutamatergic processes, and the expression of extinction, known to be affected by GABAergic agents such as chlordiazepoxide.


Assuntos
Monoterpenos Acíclicos/farmacologia , Condicionamento Operante/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Monoterpenos Acíclicos/metabolismo , Animais , Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Clordiazepóxido/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Braz J Med Biol Res ; 52(11): e8899, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31664307

RESUMO

Few behavioral tests allow measuring several characteristics and most require training, complex analyses, and/or are time-consuming. We present an apparatus based on rat exploratory behavior. Composed of three different environments, it allows the assessment of more than one behavioral characteristic in a short 3-min session. Factorial analyses have defined three behavioral dimensions, which we named Exploration, Impulsivity, and Self-protection. Behaviors composing the Exploration factor were increased by chlordiazepoxide and apomorphine and decreased by pentylenetetrazole. Behaviors composing the Impulsivity factor were increased by chlordiazepoxide, apomorphine, and both acute and chronic imipramine treatments. Behaviors composing the Self-protection factor were decreased by apomorphine. We submitted Wistar rats to the open-field test, the elevated-plus maze, and to the apparatus we are proposing. Measures related to exploratory behavior in all three tests were correlated. Measures composing the factors Impulsivity and Self-protection did not correlate with any measures from the two standard tests. Also, compared with existing impulsivity tests, the one we proposed did not require previous learning, training, or sophisticated analysis. Exploration measures from our test are as easy to obtain as the ones from other standard tests. Thus, we have proposed an apparatus that measured three different behavioral characteristics, was simple and fast, did not require subjects to be submitted to previous learning or training, was sensitive to drug treatments, and did not require sophisticated data analyses.


Assuntos
Ansiedade/psicologia , Comportamento Animal/fisiologia , Pesquisa Comportamental/instrumentação , Comportamento Exploratório/fisiologia , Medo/fisiologia , Comportamento Impulsivo/fisiologia , Animais , Ansiolíticos/farmacologia , Antidepressivos Tricíclicos/farmacologia , Apomorfina/farmacologia , Comportamento Animal/efeitos dos fármacos , Clordiazepóxido/farmacologia , Agonistas de Dopamina/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Medo/efeitos dos fármacos , Antagonistas GABAérgicos/farmacologia , Comportamento Impulsivo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Modelos Animais , Pentilenotetrazol/farmacologia , Ratos Wistar , Fatores de Tempo
9.
Alcohol ; 81: 56-60, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31176787

RESUMO

Alcohol withdrawal syndrome (AWS) is a serious complication of abrupt alcohol cessation. Severe AWS can develop into delirium tremens (DT), which is potentially life-threatening. Lorazepam (LOR) and chlordiazepoxide (CDE) are mainstays of therapy for AWS. Current literature lacks studies comparing outcomes between the two drugs for patients who are not in a de-addiction ward specifically for withdrawal treatment. The primary objective of the study was to determine the incidence rate of DT between the groups. Of 2112 patients screened, 142 met inclusion criteria (LOR = 74, CDE = 68). Baseline characteristics were similar between groups. No significant difference in the primary outcome of DT development was observed (7% LOR, 9% CDE; p = 0.76). No significant differences in cumulative doses of scheduled LOR or CDE were observed (LOR 14.6 ± 8 mg, CDE 15.4 ± 12; p = 0.64). However, significant differences were found in the amount of "as needed" (PRN) LOR required for the two groups (LOR 3.2 ± 4 mg, CDE 6.6 ± 13 mg; p = 0.03) and the amount of scheduled plus PRN LOR required (LOR 17.7 ± 10 mg, CDE 21.9 ± 14 mg; p = 0.04). Doses are reported in LOR equivalents. There were no observed differences in duration of treatment (LOR 3.6 ± 1.3 days, CDE 3.9 ± 2.1 days; p = 0.3) or length of stay (LOR 5.28 ± 3.8 days, CDE 4.73 ± 4.2 days p = 0.4). No adverse events related to BZD were noted in either group. Hospital outcomes did not differ between the groups, but patients treated with CDE may require more adjuvant therapy to control symptoms of AWS. Both agents appear equally effective at preventing the development of DT in those patients admitted to general medicine wards.


Assuntos
Delirium por Abstinência Alcoólica/prevenção & controle , Clordiazepóxido/uso terapêutico , Etanol/efeitos adversos , Hipnóticos e Sedativos/uso terapêutico , Lorazepam/uso terapêutico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
10.
J Anal Toxicol ; 43(5): 406-410, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30796822

RESUMO

Demoxepam, when derivatized by silylation and analyzed using gas chromatography-mass spectrometry (GC-MS), produces artifacts which are falsely identified as nordiazepam and oxazepam. Demoxepam was analyzed unextracted at various concentrations, using different derivatization procedures, and on different GC-MS systems. Oxazepam and nordiazepam were consistently identified in neat demoxepam samples, despite the changing variables. Under certain conditions, oxazepam was identified as low as 50 ng/mL derivatized demoxepam, and nordiazepam identified as low as 500 ng/mL derivatized demoxepam. The analysis of underivatized demoxepam resulted in nordiazepam detection at levels ≥2,500 ng/mL, whereas oxazepam was not detectable at or below 10,000 ng/mL demoxepam. Isolating the derivatization procedures and GC-MS analyses demonstrates that these processes are responsible for any degradation or rearrangement reactions which are taking place. Laboratories which follow similar procedures for benzodiazepine confirmations should consider these findings when interpreting analytical data from chlordiazepoxide cases.


Assuntos
Benzodiazepinas/análise , Clordiazepóxido/análise , Cromatografia Gasosa-Espectrometria de Massas/normas , Nordazepam/análise , Oxazepam/análise , Reações Falso-Positivas , Humanos , Limite de Detecção , Padrões de Referência
11.
Pharmacol Biochem Behav ; 179: 43-54, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30735674

RESUMO

The behavioral effects of putative anxiolytic and anxiogenic drugs are usually evaluated in highly standardized tests. Here, we determined the effects of such drugs in rats housed in mixed sex groups in a seminatural environment. Sexually receptive female Wistar rats were treated with either the anxiolytic drug chlordiazepoxide (2 mg/kg), the anxiogenic drug yohimbine (1 mg/kg), or saline (1 ml/kg). Different emotional challenges eliciting purportedly positive affect (lavender odor, Mozart's music, chocolate flavored food) or negative affect (white noise, fox odor) were then introduced into the seminatural environment. A co-occurrence analysis revealed that music was rather aversive to the rats, as were white noise and fox odor. Lavender and chocolate exposure decreased classical indicators of fear. White noise suppressed sexual behaviors and caused avoidance of the open area. Yohimbine increased sexual receptivity during lavender exposure, decreased the latency to flee the white noise, and increased self-grooming regardless of the emotional challenge. Chlordiazepoxide was effective only during exposure to white noise, and increased the frequency of hiding alone. The modest effects of the drugs in the seminatural environment may be the result of social buffering and rats experiencing a high degree of controllability over their environment.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Ansiolíticos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Clordiazepóxido/farmacologia , Estro , Ioimbina/farmacologia , Animais , Feminino , Masculino , Ratos , Ratos Wistar
12.
Behav Pharmacol ; 30(2 and 3-Spec Issue): 208-219, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30169377

RESUMO

The extent to which rats express anxiety-like behavior on the elevated plus-maze (EPM) depends on their previous maze experience. Open-arm avoidance develops in maze-experienced rats, and is often accompanied by a diminished anxiolytic response to benzodiazepines. Regions of the dorsal raphe nucleus (DRN) were examined in male Sprague-Dawley rats using c-Fos and serotonin immunohistochemistry following a single exposure, a second exposure or no exposure to the EPM. We then examined the effect of the benzodiazepine anxiolytic chlordiazepoxide (CDP, 5 mg/kg) on EPM behavior and DRN neural activity. Enhanced open-arm avoidance was evident on the second EPM trial in both experiments. The observed pattern of c-Fos expression suggests that the first exposure to the maze activates serotonin cells in the rostral and dorsal regions of the DRN and that only the dorsal subregion is activated by a second exposure. CDP increased open-arm exploration during the first trial, which corresponded to decreased 5-hydroxytryptamine (5-HT) activity in the rostral and ventral subregions of the DRN. However, 5-HT activity in the DRN was reduced in rats on the second maze trial compared with the first trial, when CDP had no effect on open-arm exploration. These results suggest that open-arm avoidance in maze-experienced rats can be characterized as a coping response that is mediated by specific populations of 5-HT neurons in the DRN.


Assuntos
Ansiedade/tratamento farmacológico , Clordiazepóxido/farmacologia , Animais , Ansiolíticos/farmacologia , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Núcleo Dorsal da Rafe/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo
13.
Braz. j. med. biol. res ; 52(11): e8899, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1039258

RESUMO

Few behavioral tests allow measuring several characteristics and most require training, complex analyses, and/or are time-consuming. We present an apparatus based on rat exploratory behavior. Composed of three different environments, it allows the assessment of more than one behavioral characteristic in a short 3-min session. Factorial analyses have defined three behavioral dimensions, which we named Exploration, Impulsivity, and Self-protection. Behaviors composing the Exploration factor were increased by chlordiazepoxide and apomorphine and decreased by pentylenetetrazole. Behaviors composing the Impulsivity factor were increased by chlordiazepoxide, apomorphine, and both acute and chronic imipramine treatments. Behaviors composing the Self-protection factor were decreased by apomorphine. We submitted Wistar rats to the open-field test, the elevated-plus maze, and to the apparatus we are proposing. Measures related to exploratory behavior in all three tests were correlated. Measures composing the factors Impulsivity and Self-protection did not correlate with any measures from the two standard tests. Also, compared with existing impulsivity tests, the one we proposed did not require previous learning, training, or sophisticated analysis. Exploration measures from our test are as easy to obtain as the ones from other standard tests. Thus, we have proposed an apparatus that measured three different behavioral characteristics, was simple and fast, did not require subjects to be submitted to previous learning or training, was sensitive to drug treatments, and did not require sophisticated data analyses.


Assuntos
Animais , Masculino , Ansiedade/psicologia , Comportamento Animal/fisiologia , Pesquisa Comportamental/instrumentação , Comportamento Exploratório/fisiologia , Medo/fisiologia , Comportamento Impulsivo/fisiologia , Fatores de Tempo , Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Apomorfina/farmacologia , Clordiazepóxido/farmacologia , Ratos Wistar , Aprendizagem em Labirinto/efeitos dos fármacos , Antagonistas GABAérgicos/farmacologia , Agonistas de Dopamina/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Medo/efeitos dos fármacos , Comportamento Impulsivo/efeitos dos fármacos , Antidepressivos Tricíclicos/farmacologia
14.
Behav Brain Res ; 353: 57-61, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29969605

RESUMO

This study evaluated the extent to which a reduction in contextual fear contributes to the anxiolytic effect of benzodiazepines in the fear-potentiated startle response. To this end, chlordiazepoxide, an anxiolytic often used as positive control in preclinical drug studies, and zolpidem, known to have sedative properties and to be devoid of anxiolytic effects, were tested in two contexts: the same context as training had taken place and an alternative context. In addition, the level of muscle relaxation was assessed in a grip strength test. Chlordiazepoxide (2.5-10 mg/kg) decreased the fear-potentiated startle response, confirming its anxiolytic activity. In addition, it dose-dependently decreased the overall startle response in the same, but not the alternative context, and did not affect grip strength, indicating that chlordiazepoxide inhibits contextual fear in the absence of non-specific drug effects. Zolpidem (1.0-10 mg/kg) reduced the overall startle response in both contexts equally and decreased grip strength, indicating that its effects on fear-potentiated startle are due to non-specific drug effects, and not anxiolytic effects. The present findings show that chlordiazepoxide reduces contextual conditioned fear in the absence of non-specific drug effects. In addition, they show that training and testing rats in different contexts makes it possible to distinguish between cued, contextual and non-specific drug effects. As exaggerated contextual fear conditioning contributes to the fear generalization processes implicated in pathological anxiety, focus in screening of anxiolytic effects could be directed more towards the suppression of contextual fear and, therefore, this approach would be a valuable addition to standard preclinical screening.


Assuntos
Ansiolíticos/farmacologia , Clordiazepóxido/farmacologia , Medo/efeitos dos fármacos , Reflexo de Sobressalto/efeitos dos fármacos , Animais , Condicionamento Psicológico/efeitos dos fármacos , Sinais (Psicologia) , Relação Dose-Resposta a Droga , Meio Ambiente , Masculino , Força Muscular/efeitos dos fármacos , Piridinas/farmacologia , Distribuição Aleatória , Ratos Wistar , Zolpidem
15.
Behav Brain Res ; 351: 24-33, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29803653

RESUMO

The prevalence of anxiety disorders is higher in women than in men. Yet preclinical studies on anxiety are mostly performed in male subjects. This may have limited our understanding of mechanisms contributing to anxiety disorders. Since fear conditioning is considered an important factor in the etiology of anxiety disorders, the present study aimed to investigate the effect of sex and estrous cycle on conditioned fear and the anxiolytic effect of benzodiazepines in rats. We measured the fear-potentiated startle response in male and female rats during different estrous cycle stages and performed a replication study in a separate cohort. In addition, we assessed the response to diazepam (0-3.0 mg/kg IP) and chlordiazepoxide (0-10 mg/kg IP) in male and female rats in proestrous/estrous and diestrous stage. Our results showed that there were no sex differences in the expression of fear-potentiated startle. The estrous cycle also did not affect the fear-potentiated startle response. In addition, male and female rats did not differ in their fear-potentiated startle response following treatment with either diazepam or chlordiazepoxide. In conclusion, the current study shows that male and female rats do not differ in their conditioned fear response and the responsiveness to benzodiazepines. The results further indicate that conditioned fear-related processes are not affected by gonadal hormone fluctuations in this paradigm. These findings may suggest that the higher prevalence of anxiety disorders in women more likely results from differences in responding to previous experiences or differences in other predisposing factors, rather than differences in conditioned fear per se.


Assuntos
Ciclo Estral , Medo/fisiologia , Reflexo de Sobressalto/fisiologia , Caracteres Sexuais , Animais , Ansiolíticos/farmacologia , Clordiazepóxido/farmacologia , Diazepam/farmacologia , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/fisiologia , Medo/efeitos dos fármacos , Feminino , Masculino , Ratos Wistar , Reflexo de Sobressalto/efeitos dos fármacos
16.
J AOAC Int ; 101(3): 714-722, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28927485

RESUMO

Two simple and accurate chemometric-assisted spectrophotometric models were developed and validated for the simultaneous determination of chlordiazepoxide (CDZ) and clidinium bromide (CDB) in the presence of an alkali-induced degradation product of CDB in their pure and pharmaceutical formulation. Resolution was accomplished by using two multivariate calibration models, including principal component regression (PCR) and partial least-squares (PLS), applied to the UV spectra of the mixtures. Great improvement in the predictive abilities of these multivariate calibrations was observed. A calibration set was constructed and the best model used to predict the concentrations of the studied drugs. CDZ and CDB were analyzed with mean accuracies of 99.84 ± 1.41 and 99.81 ± 0.89% for CDZ and 99.56 ± 1.43 and 99.44 ± 1.41% for CDB using PLS and PCR models, respectively. The proposed models were validated and applied for the analysis of a commercial formulation and laboratory-prepared mixtures. The developed models were statistically compared with those of the official and reported methods with no significant differences observed. The models can be used for the routine analysis of both drugs in QC laboratories.


Assuntos
Clordiazepóxido/análise , Quinuclidinil Benzilato/análogos & derivados , Espectrofotometria Ultravioleta/métodos , Benzilatos/química , Calibragem , Estabilidade de Medicamentos , Hidrólise , Análise dos Mínimos Quadrados , Análise de Componente Principal , Quinuclidinil Benzilato/análise , Quinuclidinil Benzilato/química , Reprodutibilidade dos Testes , Hidróxido de Sódio/química
17.
Clin Imaging ; 48: 22-25, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29028509

RESUMO

Anoxic brain injury can manifest with various abnormal movements. We describe acute chorea in a young patient with anoxic brain injury due to chlordiazepoxide toxicity who had delayed radiographic lesions in bilateral globus pallidus. Although brain MRI 8days after the anoxic event was unremarkable, repeat brain MRI 15days after the event showed T2 hyperintensities and enhancement within the bilateral globus pallidi. It is possible that MRI brain findings of bilateral basal ganglia lesions may appear later than onset of chorea in anoxic brain injury. However, given the normal brain MRI in between, other etiologies cannot be excluded entirely.


Assuntos
Encéfalo/patologia , Clordiazepóxido/efeitos adversos , Coreia/etiologia , Hipóxia Encefálica/complicações , Adulto , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologia , Encéfalo/diagnóstico por imagem , Lesões Encefálicas , Coreia/diagnóstico por imagem , Globo Pálido/diagnóstico por imagem , Globo Pálido/patologia , Humanos , Hipóxia , Hipóxia Encefálica/induzido quimicamente , Hipóxia Encefálica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino
18.
Biol Psychiatry ; 83(1): 9-17, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28888327

RESUMO

BACKGROUND: Stress is a prevailing risk factor for mood-related illnesses, wherein women represent the majority of those affected by major depression. Despite the growing literature suggesting that affective disorders can arise after a traumatic event is vicariously experienced, this relationship remains understudied in female subjects at the preclinical level. Thus, the objective of the current investigation was to examine whether exposure to emotional and/or psychological stress (ES) mediates depression-related outcomes in female mice. METHODS: Female C57BL/6 mice (8 weeks old, null parity) vicariously experienced the defeat bout of a male conspecific, by a male CD1 aggressor, for 10 consecutive days. Twenty-four hours after the last stress exposure, female mice were tested in the social interaction, sucrose preference, tail suspension, or elevated plus maze tests. Furthermore, we examined whether ketamine and chlordiazepoxide, pharmacological agents used to treat mood-related disorders in the clinical population, would reverse the ES-induced social dysfunction. RESULTS: When compared with control mice, female mice exposed to ES displayed decreased social behavior and preference for sucrose, along with increased immobility in the tail suspension test. Also, they displayed higher levels of blood serum corticosterone, as well as decreased body weight. Lastly, the ES-induced avoidance-like phenotype was ameliorated by both ketamine and chlordiazepoxide. CONCLUSIONS: Our data indicate that female mice exposed to ES display a behavioral and physiologic profile that mimics symptoms of depression in the clinical population. As such, this experimental model may be adopted to examine vicarious stress-induced mood-related disorders, as well as pharmacological antidepressant response, in a sex-specific manner.


Assuntos
Transtorno Depressivo/etiologia , Dominação-Subordinação , Estresse Psicológico/etiologia , Animais , Antidepressivos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Peso Corporal , Clordiazepóxido/farmacologia , Corticosterona/sangue , Transtorno Depressivo/sangue , Transtorno Depressivo/tratamento farmacológico , Sacarose na Dieta , Modelos Animais de Doenças , Exposição à Violência , Feminino , Ketamina/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Testes Psicológicos , Estresse Psicológico/sangue , Estresse Psicológico/tratamento farmacológico , Percepção Gustatória/efeitos dos fármacos , Percepção Visual
19.
Am J Ther ; 25(2): e267-e269, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29189312

RESUMO

CLINICAL FEATURES: We present a case of a middle-aged man admitted to an inpatient detoxification facility for withdrawal of intranasal heroin, alprazolam, and ethanol. The patient was placed on methadone and chlordiazepoxide tapers. Ondansetron and trazodone were prescribed as needed for symptom control. On the third hospital day, the patient was found unresponsive with blood glucose of 40 mg/dL. He had no history of glucose dysregulation. The patient was pronounced dead shortly thereafter. Methadone overdose was ruled the cause of death. THERAPEUTIC CHALLENGES: There have been studies linking methadone with glucose dysregulation. Hypoglycemia can induce changes in the electrical system in the heart, including lengthening QT interval, lengthening repolarization, and causing ST wave changes. In addition, there have been studies linking methadone treatment to QT interval prolongation and torsade de pointes. Ondansetron and trazodone have both been associated with cardiac conduction abnormalities. SOLUTION: We recommend initial blood glucose and cardiac monitoring in patients taking methadone 40 mg daily or higher.


Assuntos
Analgésicos Opioides/envenenamento , Morte Súbita/etiologia , Hipoglicemia/induzido quimicamente , Metadona/envenenamento , Tratamento de Substituição de Opiáceos/efeitos adversos , Analgésicos Opioides/administração & dosagem , Glicemia , Clordiazepóxido/uso terapêutico , Overdose de Drogas/sangue , Overdose de Drogas/etiologia , Humanos , Masculino , Metadona/administração & dosagem , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Substâncias/reabilitação
20.
J Neurosci Methods ; 293: 37-44, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28847697

RESUMO

BACKGROUND: In studies that measure social behavior of a freely interacting pair rats social behavior of one rat is strongly influenced by the behavior of the other. This prevents evaluating social behavior of one single rat. NEW METHOD: We assessed the motivation to interact socially in a modified open-field, by measuring the time a rat attempted to interact with a co-specific separated by a grid in a birdcage outside of the apparatus. We propose time in front of the birdcage is an indicator of social behavior. RESULTS: We showed that the focal rat allocates more time in front of the birdcage, interacting with another rat through the grid. Also, that the presence of the other rat that attracts the focal rat. Habituation to the apparatus, repeated testing and illumination condition did not alter the proximity measures of rats. Finally, treatment with chlordiazepoxide (3.0mg/kg) either increased the time spent in front of the cage by males and females or (5.6mg/kg) increased the proximity measure of females. COMPARING WITH EXISTING METHOD: Our method prevents partners from influencing the target rat's social behavior; existing methods do not. Also, it is more sensitive to the effect of chlordiazepoxide than the broadly used method proposed by File and Hyde (1978). CONCLUSIONS: Proximity is an advantageous measure: it allows the assessment of only one focal animal without the interference of a partner; it is simple to take; it requires little interpretation skills or training from the experimenter, no special equipment or conditions.


Assuntos
Comportamento Animal , Modelos Psicológicos , Ratos Wistar/psicologia , Comportamento Social , Comportamento Espacial , Animais , Comportamento Animal/efeitos dos fármacos , Clordiazepóxido/farmacologia , Feminino , Habituação Psicofisiológica , Iluminação , Masculino , Motivação/efeitos dos fármacos , Testes Psicológicos , Psicotrópicos/farmacologia , Distribuição Aleatória , Reprodutibilidade dos Testes , Comportamento Espacial/efeitos dos fármacos , Fatores de Tempo
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