Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.510
Filtrar
1.
Anesth Analg ; 130(1): 224-232, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31498189

RESUMO

BACKGROUND: In the perioperative context, benzodiazepines are widely used as anxiolytics. They affect cognition in general, but it is unclear whether the effects of a small dose of the short-acting benzodiazepine midazolam can be assessed objectively. To address this scientific question, we conducted a prospective observational study in adults 55-73 years of age. Using both validated psychometric and functional imaging techniques, we determined whether a 2-mg intravenous (IV) dose of midazolam affects cognitive function. METHODS: We measured the effect of 2 mg IV of midazolam with both the well-established Repeatable Battery for the Assessment of Neuropsychological Status test and resting-state functional magnetic imaging (rs-fMRI) in older adults. RESULTS: Midazolam reduces immediate and delayed memory and has a profound and robust effect on rs-fMRI. Baseline resting-state connectivity predicts memory decline after midazolam administration. CONCLUSIONS: Observed effects of midazolam on brain networks were statistically significant even in a small group of volunteers. If validated by other investigators, resting-state brain connectivity may have utility as a measure to predict sensitivity to midazolam in older adults.


Assuntos
Ansiolíticos/administração & dosagem , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Midazolam/administração & dosagem , Fatores Etários , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Feminino , Humanos , Infusões Intravenosas , Imagem por Ressonância Magnética , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Repressão Psicológica
2.
Medicine (Baltimore) ; 98(51): e18188, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860965

RESUMO

AIM: We compared the effects of 50% N2O and N2O titration in burn management to alleviate pain and anxiety associated with burn dressing. METHODS: In this single-blind prospective randomized controlled trial, 70 stable adult burn patients were randomized to 2 groups during May 2015 to January 2016. The experimental group was titrated with N2O ranging from 30% to the ideal sedation concentration before dressing change until the end. The control group was treated with 50% N2O 2 minutes before dressing change until the end. Pain, anxiety, vital signs, and the highest concentrations of N2O inhaled were recorded at 1 minute before N2O inhalation (T0), dismantling of outer (T1), inner dressings (T2), debridement (T3), drug-smearing (T4), bandaging (T5), and 10 minutes after completion of the procedure (T6). RESULTS: The pain and anxiety scores in the experimental group performed significantly less than the control group during T2-T6. The systolic blood pressure in T2 and the heart rate at T2 and T3 varied significantly between the 2 groups. The highest N2O concentrations of the experimental group were mainly 60% to 70% at T2 (87.9%), T3 (87.9%), and T4 (81.8%). CONCLUSION: N2O titration significantly reduced pain and anxiety in burn patients, with minimal side effects.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Ansiolíticos/uso terapêutico , Queimaduras/terapia , Óxido Nitroso/uso terapêutico , Administração por Inalação , Adolescente , Adulto , Idoso , Analgésicos não Entorpecentes/administração & dosagem , Ansiolíticos/administração & dosagem , Ansiedade/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nitroso/administração & dosagem , Manejo da Dor , Método Simples-Cego , Adulto Jovem
3.
Int J Clin Pharm ; 41(6): 1526-1535, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31595447

RESUMO

Background Benzodiazepines are commonly prescribed medications, especially among elderly, despite known risks and guidelines focused on short term usage. There is an increased trend of benzodiazepine consumption in Croatia. Consumption of anxiolytics in 2015 and 2016 in Croatia can almost entirely be ascribed to benzodiazepines, with diazepam being the most commonly prescribed drug, followed by alprazolam. Objective The aim of this study was to examine benzodiazepine utilization habits among the Croatian population. Setting This study was conducted on the national level, based on digital prescribing data. Method Data regarding the prescription of anxiolytics in Croatia was sourced and analyzed from the Croatian Health Insurance Fund database for the years 2015 and 2016. Drugs included in the study were classified according to The Anatomical and Therapeutic Classification of Medicines System, and consist of several chemical therapeutic subgroups (N05BA, N05BC, N05CD, N05CF). Main outcome measures The prescribing frequency of the most often prescribed benzodiazepines in Croatia. Results The total number of benzodiazepine prescriptions was 5,085,695 in 2015, and 5,294,075 in 2016; this represents a 208,380 increase in prescriptions, or 4.1% more than the previous year. The number of patients who utilized benzodiazepines showed an increase from 860,664 (8.67%) in 2015 to 876,046 (8.76%) in 2016. In relation to gender, benzodiazepine consumption was higher among female patients in all age groups, with the number of utilized benzodiazepine prescriptions per patient being highest in the oldest age group (80 +), comprising 7 prescriptions per patient in a 12 months period. Conclusion Increased utilization and long-term treatment with benzodiazepines remains a serious challenge for the health care system in Croatia. National prescription guidelines, improved control of benzodiazepine usage and prescriptions, along with restricted release drug lists, should all be considered as potential measures to rationalize benzodiazepine prescription, control unnecessary expenditure in the country and improve the well-being of the patients.


Assuntos
Ansiolíticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Padrões de Prática Médica/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Croácia , Bases de Dados Factuais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Fatores Sexuais , Adulto Jovem
4.
J Pharm Pharmacol ; 71(12): 1879-1889, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31595522

RESUMO

OBJECTIVES: The study aimed to identify nutmeg compounds that indirectly interact with the endocannabinoid system through inhibition of the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes. METHODS: Thirteen compounds were screened for FAAH and MAGL inhibition. Compounds demonstrating significant FAAH inhibition were evaluated to determine the halfmaximal inhibitory concentration (IC50 ). The most potent compound was investigated in the elevated plus maze (EPM) rodent anxiety model. KEY FINDINGS: Three compounds, licarin A (9), 5'-methoxylicarin A (8) and malabaricone C (6) were most active in inhibiting FAAH with IC50 of 7.02 µm ± 2.02, 4.57 µm ± 0.66 and 38.29 µm ± 6.18, respectively. None of the purified compounds showed significant MAGL inhibition. Because of its relative high potency and selectivity, compound 8 was further evaluated in the EPM animal model of anxiety. The compound showed significant increase in number of open arm entries (P < 0.05) when administered at 120 mg/kg dose. No effect was observed on the locomotor activity. CONCLUSIONS: Results collected introduce active nutmeg compounds as potential leads for further development. Of the three compounds, 8 possesses highest potency and FAAH selectivity as well as anxiolytic activity. Furthermore, in vivo testing in appropriate behavioural animal paradigms is warranted.


Assuntos
Endocanabinoides/metabolismo , Inibidores Enzimáticos/farmacologia , Myristica/química , Fenóis/farmacologia , Amidoidrolases/antagonistas & inibidores , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/isolamento & purificação , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/isolamento & purificação , Concentração Inibidora 50 , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Monoacilglicerol Lipases/antagonistas & inibidores , Fenóis/administração & dosagem , Fenóis/isolamento & purificação
5.
Int J Neuropsychopharmacol ; 22(11): 735-745, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31613314

RESUMO

BACKGROUND: New treatments for stress-related disorders including depression, anxiety, and substance use disorder are greatly needed. Kappa opioid receptors are expressed in the central nervous system, including areas implicated in analgesia and affective state. Although kappa opioid receptor agonists share the antinociceptive effects of mu opioid receptor agonists, they also tend to produce negative affective states. In contrast, selective kappa opioid receptor antagonists have antidepressant- and anxiolytic-like effects, stimulating interest in their therapeutic potential. The prototypical kappa opioid receptor antagonists (e.g., norBNI, JDTic) have an exceptionally long duration of action that complicates their use in humans, particularly in tests to establish safety. This study was designed to test dose- and time-course effects of novel kappa opioid receptor antagonists with the goal of identifying short-acting lead compounds for future medication development. METHODS: We screened 2 novel, highly selective kappa opioid receptor antagonists (CYM-52220 and CYM-52288) with oral efficacy in the warm water tail flick assay in rats to determine initial dose and time course effects. For comparison, we tested existing kappa opioid receptor antagonists JDTic and LY-2456302 (also known as CERC-501 or JNJ-67953964). RESULTS: In the tail flick assay, the rank order of duration of action for the antagonists was LY-2456302 < CYM-52288 < CYM-52220 << JDTic. Furthermore, LY-2456302 blocked the depressive (anhedonia-producing) effects of the kappa opioid receptor agonist U50,488 in the intracranial self-stimulation paradigm, albeit at a higher dose than that needed for analgesic blockade in the tail flick assay. CONCLUSIONS: These results suggest that structurally diverse kappa opioid receptor antagonists can have short-acting effects and that LY-2456302 reduces anhedonia as measured in the intracranial self-stimulation test.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Analgésicos não Entorpecentes/farmacologia , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzamidas/farmacologia , Antagonistas de Entorpecentes/farmacologia , Piperidinas/farmacologia , Pirrolidinas/farmacologia , Receptores Opioides kappa/antagonistas & inibidores , Tetra-Hidroisoquinolinas/farmacologia , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/administração & dosagem , Analgésicos não Entorpecentes/administração & dosagem , Animais , Ansiolíticos/administração & dosagem , Antidepressivos/administração & dosagem , Benzamidas/administração & dosagem , Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Masculino , Antagonistas de Entorpecentes/administração & dosagem , Piperidinas/administração & dosagem , Pirrolidinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/agonistas , Tetra-Hidroisoquinolinas/administração & dosagem
6.
Expert Opin Investig Drugs ; 28(11): 1003-1012, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31607187

RESUMO

Introduction: Generalized anxiety disorder (GAD) is a common and disabling psychiatric condition that affects 3% of the population and exacts significant costs to society if untreated. There are numerous treatment options available, but all have side effects, and none are reliably effective; hence, there is a significant need for new medications.Areas covered: The authors reviewed clinical Phase II and III studies listed on the clinicaltrials.gov and clinicaltrialsregister.eu websites, 2007-present. Additional information was gathered from the study sponsor websites and Pubmed. The categories of mechanisms investigated include: modulators of GABAergic or glutamatergic activity; modulators of monoaminergic systems including serotonin, norepinephrine, and dopamine; and modulators of neuropeptide corticotropin release factor.Expert opinion: There are few investigational drugs in the later stages of clinical development. Challenges include high placebo response rates, enrollment of symptomatic volunteers with minimal depressive and anxiety comorbidity, and the lack of a unifying pathophysiological model. Drug developers should consider implementing trial designs such as sequential parallel comparison design to enhance signal detection. Inclusion of depressive comorbidity may also enhance signal detection by reducing placebo-responsivity. More studies examining glutamate-mediated neuroplasticity in GAD are needed.


Assuntos
Ansiolíticos/administração & dosagem , Transtornos de Ansiedade/tratamento farmacológico , Drogas em Investigação/administração & dosagem , Animais , Ansiolíticos/farmacologia , Transtornos de Ansiedade/fisiopatologia , Desenvolvimento de Medicamentos , Drogas em Investigação/farmacologia , Humanos , Projetos de Pesquisa
8.
Pan Afr Med J ; 33: 117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489095

RESUMO

Catatonia occurring as part of a clinical picture of dementia has been reported with almost all types of dementia. It remains under-diagnosed in older adults and those with dementia. We review a case of a young patient admitted in our psychiatric department for catatonia and after efficient treatment with Lorazepam, assessment revealed a dementia. Catatonia is a severe neuropsychiatric syndrome with an excellent prognosis if recognized and treated without delay.


Assuntos
Ansiolíticos/administração & dosagem , Catatonia/tratamento farmacológico , Demência/diagnóstico , Lorazepam/administração & dosagem , Catatonia/etiologia , Demência/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
9.
Pharmacol Biochem Behav ; 185: 172761, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31425712

RESUMO

Alcohol use is frequently associated with mood disorders. Similarly, individuals suffering from these disorders have a higher risk of developing alcoholism. Several reports have implicated orexin signaling in different behaviors related to alcohol consumption, whereas antagonists block these actions. However, the involvement of orexin-1-receptor (Orx1R) in ethanol-induced anxiolysis remains relatively unexplored. The purpose of this study was to investigate whether intra-accumbal inhibition of Orx1R blocks the anxiolytic-like effect of ethanol and to determine if ethanol administration modifies orexin-A content and Orx1R expression in the nucleus accumbens (NAc). The elevated-plus-maze test (EPM-test) was used to measure anxiety; orexin-A content and Orx1R expression were determined by enzyme-immunoassay and western blot, respectively. The results showed that the pretreatment with a selective antagonist of Orx1R, SB-334867 (SB, 3 µg/side), prevents the anxiolytic-like behavior induced by acute ethanol (2.5 g/kg). SB-334867 per se had no effect on anxiety levels. Pretreatment with SB-334867 followed by ethanol (SB + Et) increased orexin-A content and Orx1R levels in the NAc in comparison to the groups that only received ethanol (V + Et) or SB-334867 (SB + S). Ethanol treatment significantly augmented Orx1R expression but not the peptide content. The increase in orexin-A observed in SB + Et animals could be due in part to the inhibition of Orx1R, since SB-334867 prevents the binding of orexin-A to the receptor. This increase in orexin-A may, in turn, induce an up-regulation of receptor. Other possible explanations were discussed. In general, these findings suggest that orexin-A contributes largely to expression of ethanol-induced anxiolytic-like effect through the signaling of Orx1R in the NAc.


Assuntos
Ansiolíticos/farmacologia , Benzoxazóis/farmacologia , Etanol/farmacologia , Naftiridinas/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Antagonistas dos Receptores de Orexina/farmacologia , Receptores de Orexina/metabolismo , Orexinas/metabolismo , Ureia/análogos & derivados , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/psicologia , Animais , Ansiolíticos/administração & dosagem , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Benzoxazóis/administração & dosagem , Etanol/administração & dosagem , Modelos Lineares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Naftiridinas/administração & dosagem , Núcleo Accumbens/metabolismo , Antagonistas dos Receptores de Orexina/administração & dosagem , Ratos , Ratos Wistar , Regulação para Cima/efeitos dos fármacos , Ureia/administração & dosagem , Ureia/farmacologia
10.
Anesth Analg ; 129(4): 1118-1123, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295177

RESUMO

BACKGROUND: Unconscious racial bias in anesthesia care has been shown to exist. We hypothesized that black children may undergo inhalation induction less often, receive less support from child life, have fewer opportunities to have a family member present for induction, and receive premedication with oral midazolam less often. METHODS: We retrospectively collected data on those <18 years of age from January 1, 2012 to January 1, 2018 including age, sex, race, height, weight, American Society of Anesthesiologists (ASA) physical status, surgical service, and deidentified anesthesiology attending physician. Outcome data included mask versus intravenous induction, midazolam premedication, child life consultation, and family member presence. Racial differences between all outcomes were assessed in the cohort using a multivariable logistic regression model. RESULTS: A total of 33,717 Caucasian and 3901 black children were eligible for the study. For the primary outcome, black children 10-14 years were 1.3 times more likely than Caucasian children to receive mask induction (adjusted odds ratio [AOR], 1.3; 95% confidence interval [CI], 1.1-1.6; P = .001). Child life consultation was poorly documented (<0.5%) and not analyzed. Black children <15 years of age were at least 31% less likely than Caucasians to have a family member present for induction (AOR range, 0.4-0.6; 95% CI range, 0.31-0.84; P < .010). Black children <5 years of age were 13% less likely than Caucasians to have midazolam given preoperatively (AOR, 0.9; 95% CI, 0.8-0.9; P = .012). CONCLUSIONS: This study suggests that disparities in strategies for mitigating anxiety in the peri-induction period exist and adultification may be 1 cause for this bias. Black children 10 to 14 years of age are 1.3 times as likely as their Caucasian peers to be offered inhalation induction to reduce anxiety. However, black children are less likely to receive premedication with midazolam in the perioperative period or to have family members present at induction. The cause of this difference is unclear, and further prospective studies are needed to fully understand this difference.


Assuntos
Afro-Americanos , Anestesia Geral , Ansiedade/prevenção & controle , Grupo com Ancestrais do Continente Europeu , Disparidades em Assistência à Saúde/etnologia , Procedimentos Cirúrgicos Operatórios , Administração Oral , Adolescente , Comportamento do Adolescente/etnologia , Fatores Etários , Anestesia Geral/efeitos adversos , Anestesia Geral/psicologia , Ansiolíticos/administração & dosagem , Ansiedade/etnologia , Ansiedade/psicologia , Criança , Comportamento Infantil/etnologia , Feminino , Humanos , Masculino , Midazolam/administração & dosagem , Pré-Medicação , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/psicologia
11.
Psychopharmacology (Berl) ; 236(8): 2527-2541, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31286156

RESUMO

RATIONALE: In conflict-based anxiety tests, rodents decide between actions with simultaneous rewarding and aversive outcomes. In humans, computerised operant conflict tests have identified response choice, latency, and vigour as distinct behavioural components. Animal operant conflict tests for measurement of these components would facilitate translational study. OBJECTIVES: In C57BL/6 mice, two operant conflict tests for measurement of response choice, latency, and vigour were established, and effects of chlordiazepoxide (CDZ) thereon investigated. METHODS: Mice were moderately diet-restricted to increase sucrose reward salience. A 1-lever test required responding under medium-effort reward/threat conditions of variable ratio 2-10 resulting in sucrose at p = 0.7 and footshock at p = 0.3. A 2-lever test mandated a choice between low-effort reward/threat with a fixed-ratio (FR) 2 lever yielding sucrose at p = 0.7 and footshock at p = 0.3 versus high-effort reward/no threat with a FR 20 lever yielding sucrose at p = 1. RESULTS: In the 1-lever test, CDZ (7.5 or 15 mg/kg i.p.) reduced post-trial pause (response latency) following either sucrose or footshock and reduced inter-response interval (increased response vigour) after footshock. In the 2-lever test, mice favoured the FR2 lever and particularly at post-reward trials. CDZ increased choice of FR2 and FR20 responding after footshock, reduced response latency overall, and increased response vigour at the FR2 lever and after footshock specifically. CONCLUSIONS: Mouse operant conflict tests, especially 2-lever choice, allow for the translational study of distinct anxiety components. CDZ influences each component by ameliorating the impact of both previous punishment and potential future punishment.


Assuntos
Ansiedade/psicologia , Condicionamento Operante/fisiologia , Conflito Psicológico , Recompensa , Pesquisa Médica Translacional/métodos , Animais , Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Condicionamento Operante/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Punição/psicologia , Sacarose/administração & dosagem
12.
Pharmacol Biochem Behav ; 184: 172740, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31326461

RESUMO

BACKGROUND: Alcohol use disorder is a serious illness marked by uncontrollable drinking and a negative withdrawal state when not using. Alcohol is one of the most commonly used drugs among adolescent populations. Given that adolescence is a unique developmental stage during which alcohol has long-term effects on future drug-taking behavior; it is essential to understand how early exposure to ethanol during adolescence may affect the abuse liability of the drug later in life. Our studies focused on characterizing how exposure to alcohol in adolescence alters later adult alcohol dependence behaviors, by using well-established mouse models of ethanol drinking. We hypothesized that early exposure to ethanol leads to increased ethanol intake in adults and other behavioral phenotypes that may lead to dependence. METHODS: We investigated the impact of ethanol drinking in early adolescent C57BL/6J mice using a modified Drinking in the Dark (DID) model. RESULTS: Our results showed that exposure to ethanol during adolescence enhanced ethanol intake in adulthood in the DID, and the 2-bottle choice drinking paradigms. In contrast, adult exposure of alcohol did not enhance later alcohol intake. We also conducted tests for ethanol behavioral sensitivity such as loss of righting reflex and anxiety-related behaviors to further elucidate the relationship between adolescent ethanol exposure and enhanced ethanol intake in adult mice. CONCLUSIONS: Overall, our results suggest that adolescence is a critical period of sensitivity and binge drinking that can lead to lasting changes in ethanol intake in adulthood. Further research will be required in order to more fully examine the neurochemical mechanisms underlying the lasting changes in adulthood.


Assuntos
Alcoolismo/psicologia , Ansiolíticos/farmacologia , Bebedeira/psicologia , Etanol/farmacologia , Fatores Etários , Animais , Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Concentração Alcoólica no Sangue , Comportamento de Escolha , Estudos de Coortes , Etanol/administração & dosagem , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reflexo de Endireitamento/efeitos dos fármacos
13.
BMC Complement Altern Med ; 19(1): 147, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234859

RESUMO

BACKGROUND: Ethanol withdrawal (EtOHW) anxiety is a crucial risk factor for alcoholic relapse. The neuropeptide nociceptin/orphanin FQ (N/OFQ) acts upon its receptor (NOP) to antagonize corticotropin-releasing factor (CRF) and elicit anxiolytic actions. Semen Ziziphi Spinosae (SZS), a prototypical hypnotic-sedative herb in Oriental medicine, exhibits anxiolytic effects during nicotine withdrawal by improving amygdaloid CRF/CRF1 receptor (CRFR1) signaling. Therefore, we evaluated the effects of SZS on EtOHW anxiety and the involvement of amygdaloid CRF/CRFR1 and N/OFQ/NOP pathways. METHODS: Male Sprague Dawley rats received intraperitoneal injections of 2 g/kg EtOH (20% v/v) once daily for 28 d followed by a 3-d withdrawal. During EtOHW, the rats were given once-daily intragastric treatments of a methanol extract of SZS (MESZS, 60 or 180 mg/kg/d). Anxiety-like behaviors were measured with the open field (OF) and elevated plus maze (EPM) tests, and plasma corticosterone (CORT) levels were examined by an enzyme-linked immunosorbent assay. mRNA and protein expression levels of the neuropeptides and their receptors were determined by quantitative polymerase chain reaction and Western blot assays. RESULTS: MESZS increased the distance traveled in the center zone of the OF and dose-dependently elongated the duration of staying in the center zone in EtOHW rats. MESZS increased both the number of entries into and the time spent in the open arms of the EPM by EtOHW rats. And, MESZS inhibited the over secretion of plasma CORT during EtOHW. EtOHW enhanced CRF and CRFR1 gene and protein expression in the central nucleus of the amygdala (CeA), which were inhibited by 180 mg/kg/d MESZS. EtOHW increased amygdaloid NOP mRNA and protein expression but spared N/OFQ mRNA expression, and 180 mg/kg/d MESZS further promoted these increases. Additionally, a post-MESZS intra-CeA infusion of either CRF or the selective NOP antagonist UFP-101 abolished the expected anxiolytic effect of 180 mg/kg/d MESZS. CONCLUSIONS: These results suggest that MESZS ameliorates EtOHW anxiety by improving both CRF/CRFR1 and N/OFQ/NOP transmissions in the CeA.


Assuntos
Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Núcleo Central da Amígdala/efeitos dos fármacos , Etanol/efeitos adversos , Neuropeptídeos/metabolismo , Síndrome de Abstinência a Substâncias/complicações , Ziziphus/química , Animais , Ansiedade/etiologia , Ansiedade/genética , Ansiedade/metabolismo , Núcleo Central da Amígdala/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Sementes/química
14.
Pharmacol Biochem Behav ; 183: 46-55, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31207269

RESUMO

Although the pathophysiology of major depression disorder (MDD) is still poorly understood, mounting evidence suggests that the brains of depressed patients are under oxidative stress, leading to depressive symptoms that may include anxiety and cognitive impairment. This study aimed to investigate if the seleno-organic compound 1-methyl-3-(phenylselanyl)-1H-indole (MFSeI) reverses the depression- and anxiogenic-like behaviour, cognitive impairment and oxidative stress induced by the intra-cerebroventricular injection of streptozotocin (STZ; 0.2 mg/4 µl/per mouse) in Swiss male mice. Twenty-four hours after the STZ injection, mice were treated with MFSeI (10 mg/kg, intra-gastrically), or vehicle solution, once daily for seven days. The behavioural tests were performed 30 min after the final MFSeI administration, followed by euthanasia and collection of the cerebral cortex and hippocampus. Administration of MFSeI reversed the depression- and anxiogenic-like behaviour and cognitive impairment induced by STZ, in mice. Neurochemical analyses demonstrated that MFSeI reversed the STZ-increased levels of reactive species, nitrite, lipid peroxidation and acetylcholinesterase activity in the cerebral cortex and hippocampus of mice. Moreover, a single administration of MFSeI (300 mg/kg, intra-gastrically) did not cause acute toxicity in Swiss male mice. Altogether, our data suggest that MFSeI exhibits antidepressant- and anxiolytic-like effects and improves the cognition of STZ-treated mice, without any toxicity.


Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Estresse Nitrosativo/efeitos dos fármacos , Selênio/química , Estreptozocina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Ansiolíticos/administração & dosagem , Antidepressivos/administração & dosagem , Ansiedade/tratamento farmacológico , Córtex Cerebral/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Depressão/induzido quimicamente , Hipocampo/metabolismo , Indóis/administração & dosagem , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Selênio/deficiência , Estreptozocina/administração & dosagem
15.
Psychiatry Res ; 279: 130-137, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31103345

RESUMO

Post traumatic stress disorder (PTSD) is one of the mental illness. The antidepressant-like properties of ginsenoside Rg2 (GRg2) have been shown, while little is known about its anti-PTSD-like effects. In the present study, the PTSD-associated behavioral deficits in rats were induced following exposure to single prolonged stress (SPS). The results showed that the decreased time and entries in the open arms in elevated plus maze test (EPMT) and increased freezing duration in contextual fear paradigm (CFP) were reversed by GRg2 (10 and 20 mg/kg) without affecting the locomotor activity. In addition, GRg2 (10 and 20 mg/kg) could block the decreased levels of progesterone, allopregnanolone, serotonin (5-HT), 5-Hydroxyindoleacetic acid (5-HIAA), corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH) in the brain or serum. In summary, GRg2 alleviated the PTSD-associated behavioral deficits with biosynthesis of neurosteroids, normalization of serotonergic system and HPA axis dysfunction.


Assuntos
Ansiolíticos/uso terapêutico , Ginsenosídeos/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Hormônio Adrenocorticotrópico/sangue , Animais , Ansiolíticos/administração & dosagem , Antidepressivos/uso terapêutico , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Modelos Animais de Doenças , Medo/efeitos dos fármacos , Ginsenosídeos/administração & dosagem , Ácido Hidroxi-Indolacético/sangue , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Serotonina/sangue
16.
J Zoo Wildl Med ; 50(1): 167-175, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120675

RESUMO

The intracoelomic implantation of satellite transmitters is associated with lower survival in surf scoters (Melanitta perspicillata) compared with other species of diving ducks, potentially due to physiologic alterations following physical exertion and stress caused by handling and confinement. The effect of intranasal administration of midazolam hydrochloride on survival of surf scoters surgically implanted with intracelomic transmitters was evaluated. Shortly after their capture in Forestville (QC, Canada) in the fall of 2013, 26 randomly selected adult female surf scoters were administered midazolam hydrochloride (4.6-5.9 mg/kg) intranasally. The same volume of saline (1 mL) was given to another 26 adult female surf scoters as a control group. All birds were surgically implanted with an intracoelomic transmitter equipped with a percutaneous antenna. Transmitters were programmed to transmit 2 hr each day for 30 days after implantation, and mortality was estimated for each group using the telemetry data. The association between the administration of midazolam and survival was assessed while controlling for other factors such as body mass, transmitter-mass-to-body-mass ratio, hematocrit, total solids, and duration of surgery, anesthesia, and confinement. The odds of presumed death in the saline group were 5.3 times higher than in the midazolam group (95% confidence interval: 1.7, 19.0; P = 0.004). The presumed mortality at 30 days for the midazolam group (23%) was lower than for the saline group (61%). No other variable was significantly associated with survival. These results suggest that sedation with midazolam shortly after capture increased the postsurgical survival of female surf scoters surgically implanted with intracoelomic transmitters.


Assuntos
Ansiolíticos/administração & dosagem , Patos/fisiologia , Hipnóticos e Sedativos/administração & dosagem , Longevidade/efeitos dos fármacos , Midazolam/administração & dosagem , Procedimentos Cirúrgicos Operatórios/veterinária , Telemetria/veterinária , Administração Intranasal/veterinária , Animais , Animais Selvagens/fisiologia , Feminino , Próteses e Implantes/veterinária , Telemetria/instrumentação
17.
Eur J Pharm Sci ; 135: 77-82, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31102650

RESUMO

Cytochrome P450 3A (CYP3A) isozymes metabolize about 50% of all marketed drugs. Their activity can be modulated up to 400-fold, which has great impact on individual dose requirements for CYP3A substrates. The activity of CYP3A can be monitored using the CYP3A substrate midazolam. To avoid pharmacological midazolam effects during phenotyping, a microdosing approach is preferred. However, the preparation of microdosed dosage forms remains a challenge. Fast dissolving buccal films are therefore proposed to facilitate this task. It was the aim of the present study to clinically evaluate a novel buccal film containing microdoses of midazolam for assessment of CYP3A activity. In a randomized, open-label crossover design, the pharmacokinetics of midazolam and its active hydroxy-metabolite, 1'­OH­midazolam, was assessed in 12 healthy volunteers after administration of single microdoses of midazolam (30 µg) as buccal film or buccal solution. The buccal film did rapidly disintegrate, was well tolerated, and no adverse events occurred. The film and the solution showed very similar midazolam plasma concentration-time profiles but were not bioequivalent according to EMA and FDA guidelines. For Cmax, AUC0-12h, and AUC0-∞ the geometric mean ratios of film to solution, with their 90% confidence intervals in parentheses, were 1.15 (1.00-1.32), 1.16 (1.04-1.28), and 1.19 (1.08-1.31), respectively. As a proxy for CYP3A activity, molar metabolic ratios of midazolam and 1'­OH­midazolam were analyzed over time, which revealed good correlations already 1 h or 2 h after application of the film or the solution, respectively. The tested midazolam buccal film is a convenient dosage form that facilitates administration of a phenotyping probe considerably and may potentially be used in special patient populations such as pediatric patients. Clinical Trials.gov Identifier: NCT03204578.


Assuntos
Ansiolíticos/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Hipnóticos e Sedativos/farmacocinética , Midazolam/farmacocinética , Administração Bucal , Ansiolíticos/administração & dosagem , Ansiolíticos/efeitos adversos , Área Sob a Curva , Estudos Cross-Over , Composição de Medicamentos , Interações Medicamentosas , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Midazolam/administração & dosagem , Midazolam/efeitos adversos , Absorção pela Mucosa Oral
18.
J Clin Psychopharmacol ; 39(3): 261-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939590

RESUMO

BACKGROUND: Anxiety symptoms frequently experienced by patients with a major neurocognitive disorder (NCD) are often treated with long-term benzodiazepines despite known adverse effects. Pregabalin has shown efficacy in generalized anxiety disorders but has not been studied in patients with a major NCD. The objective of this study was to describe the use of pregabalin for anxiety in patient with a major NCD and the impact of its use on the pharmacological treatment change. METHODS: A retrospective study was conducted using data of hospitalized patients in a cognitive-behavioral specialized unit between January 2015 and December 2017. Patients with a major NCD treated by pregabalin were included in this study. Data about the use of pregabalin (initiation and effective dosage, titration duration) and the use of other psychotropics were collected from the patients' medical records. RESULTS: Thirty-three patients were included (mean age, 79.6 ± 11.7 years; 66.7% women). The mean duration of pregabalin titration was 18.6 ± 1.4 days, and the mean effective dosage was 200.0 ± 130.8 mg/d (range, 50-700 mg/d). At admission (before pregabalin use), 78.8% of patients were treated with a systematic prescription of benzodiazepine. At discharge (with pregabalin use), a significant decrease in patients with systematic prescription of benzodiazepine was observed (78.8% vs 33.3%, P = 0.001). During hospitalizations, no pregabalin treatment has been discontinued for lack of efficacy or for tolerance. CONCLUSIONS: Larger controlled studies are needed to confirm the efficacy and the safety of pregabalin to treat anxiety symptoms associated with neurocognitive disorders.


Assuntos
Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Transtornos Neurocognitivos/tratamento farmacológico , Pregabalina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Relação Dose-Resposta a Droga , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/psicologia , Pregabalina/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
19.
Fortschr Neurol Psychiatr ; 87(4): 259-270, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30999380

RESUMO

Long-term prescriptions of benzodiazepines are made mainly to elderly and female patients. Withdrawal treatments should be carried out gradually over a period of several weeks. Sleep and depressive disorders during benzodiazepine withdrawal can best be treated with sedating antidepressants. The few studies on this subject suggest psychoeducation, motivational strategies and cognitive behavioural therapy as having some efficacy.


Assuntos
Ansiolíticos , Antidepressivos/uso terapêutico , Benzodiazepinas , Terapia Cognitivo-Comportamental , Hipnóticos e Sedativos/uso terapêutico , Síndrome de Abstinência a Substâncias/terapia , Ansiolíticos/administração & dosagem , Ansiolíticos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Humanos , Motivação , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/psicologia
20.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999611

RESUMO

Lysine-rich proteins are some of the most important proteins of neurons and it has become necessary to investigate the possible role of L-lysine as a brain functioning regulator. The purpose of our study is to identify the characteristics and the mechanisms of L-lysine effects on the different types of pain-induced behavior in the stimulation of tail and foot-shock models in 210 adult male Wistar rats. L-lysine was administered in intraperitoneal or intracerebroventricular injections in doses of 0.15-50.0 µg/kg. When a tail is irritated, L-lysine was found to enhance pain sensitivity and affective defense after both intraperitoneal and intracerebroventricular administration. In the case of unavoidable painful irritation of a pair of rats with both types of L-lysine administration, there was no direct correlation of the severity of pain with defensive reactions and outbursts of aggression. This indicates a more complex integration of the activity of brain structures in this situation of animal interaction, which was confirmed by the results of the direct amino acid action on the periventricular brain structures. Our findings show that L-lysine influences the selective brain activity in dependence on the biological significance of pain-induced behavior.


Assuntos
Agressão/efeitos dos fármacos , Ansiolíticos/farmacologia , Encéfalo/efeitos dos fármacos , Lisina/farmacologia , Limiar da Dor/efeitos dos fármacos , Dor/complicações , Animais , Ansiolíticos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Encéfalo/fisiologia , Lisina/administração & dosagem , Masculino , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA