Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Behav Brain Res ; 401: 113066, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33333109

RESUMO

Major depression disorder (MDD) is one of the most widespread and debilitating psychiatric diseases and may be associated with other mental disorders such as anxiety. Despite advances in neurobiology studies, currently no established mechanism can explain all facets of MDD, and available drugs often show therapeutic delay for clinical effectiveness and response rates in patients are around 50 %. Previous activities of piperazine derivatives on CNS are indicators of its therapeutic potential for treating mental disorders. In this regard, we have previously shown that the piperazine derivative 2,6-di-tert-butyl-4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)phenol (LQFM212) has anxiolytic-like activity which involves serotonergic pathway, nicotinic receptors and BZD-site of GABAA receptor, without cognitive impairments. Herein, was evaluated the potential antidepressant-like effect of LQFM212 on forced swimming test (FST) after a single dose of 54 µmol/kg and after repeated treatment for 15 days in mice. Pretreatment with WAY-100635, PCPA, prazosin, SCH-23390, sulpiride or AMPT reversed the antidepressant-like effect on FST, suggesting that monoaminergic pathway contributes for effects of LQFM212. Furthermore, repeated treatment with LQFM212 increased hippocampal BDNF levels dosed by ELISA kit. In assessment of possible adverse effects, repeated treatment with LQFM212 did not alter the body weight of the animals, glutathione levels in the liver, and serum levels of AST, ALT, urea, and creatinine. Taken together, the results showed that LQFM212 has an antidepressant-like effect that involves monoaminergic pathway and increased BDNF levels. This compound represents promising candidate for prototype of psychoactive drugs for treatment of anxiety and depression disorders since these pathological conditions may exist in comorbidities.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Monoaminas Biogênicas , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Neurotransmissores/farmacologia , Piperazinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Modelos Animais de Doenças , Masculino , Camundongos , Neurotransmissores/administração & dosagem , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos
2.
Neurochem Int ; 124: 245-255, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30685320

RESUMO

Serotonin2C receptor (5-HT2C) agonists are promising drugs for the treatment of neuropsychiatric diseases. However, their effect is not completely understood in part because they possibly affect several neurobiological networks simultaneously. We studied the effect of the 5-HT2C receptor agonist WAY-163909 (0.3 and 3 mg/kg; i.p.) on the tissue concentration of dopamine (DA), 5-HT and noradrenaline (NA) in 29 rat brain regions related to motor, cognitive, mood and vegetative networks. We found that WAY-163909, without altering the tissue concentration of NA, increased 5-HT concentrations in the medial orbitofrontal cortex and the motor cortex M2 at 3 mg/kg and decreased it in the dorsolateral orbitofrontal cortex at 0.3 mg/kg. WAY-163909 enhanced DA concentrations in the central nucleus of the amygdala at 0.3 mg/kg and reduced it in the dorsal hypothalamus at 3 mg/kg. Using correlative analysis of the tissue content of monoamines, WAY-163909 dramatically changed the profile and the pattern of the correlations within and between monoaminergic systems without drastically changing the total number of these correlations. The profile of these changes in correlations was dose-dependent as it was very different between the two doses within and among monoaminergic systems. In conclusion, the data indicated that the 5-HT2C receptor agonist WAY-163909 quantitatively alters monoamine content in very few regions but promotes multiple changes of monoaminergic connectivity in the brain.


Assuntos
Azepinas/farmacologia , Monoaminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Indóis/farmacologia , Receptor 5-HT2C de Serotonina/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Animais , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Masculino , Ratos , Ratos Sprague-Dawley
3.
Fundam Clin Pharmacol ; 27(5): 471-82, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22827775

RESUMO

Dehydrodieugenol, known as bis-eugenol, is a eugenol ortho dimer, and both compounds were able to exhibit anti-inflammatory and antioxidant activities in previous studies. Furthermore, eugenol showed antidepressant-like effect; however, the biological actions of bis-eugenol on experimental models for screening antidepressant activity are still unknown. The present study investigated a possible antidepressant-like activity of bis-eugenol in the forced swimming test (FST) and tail suspension test (TST) in mice and the involvement in the monoaminergic system in this effect. In addition, a neurochemical analysis on brain monoamines of mice acutely treated with bis-eugenol was also conducted. Bis-eugenol decreased the immobility time in the FST and TST without accompanying changes in ambulation in the open field test at 10 mg/kg, i.p.. Nevertheless, it induced ambulation at 25 and 50 mg/kg doses. The anti-immobility effect of bis-eugenol (10 and 50 mg/kg, i.p.) was prevented by pretreatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), SCH23390 (15 µg/kg, s.c., a dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist). Monoamines analysis using high-performance liquid chromatograph revealed significant increase in the 5-HT, NE and DA levels in brain striatum. The present study indicates that bis-eugenol possesses antidepressant-like activity in FST and TST by altering dopaminergic, serotonergic and noradrenergic systems function.


Assuntos
Antidepressivos/uso terapêutico , Monoaminas Biogênicas/agonistas , Corpo Estriado/efeitos dos fármacos , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Eugenol/análogos & derivados , Lignanas/uso terapêutico , Neurônios/efeitos dos fármacos , Neurônios Adrenérgicos/efeitos dos fármacos , Neurônios Adrenérgicos/metabolismo , Animais , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Antidepressivos/antagonistas & inibidores , Comportamento Animal/efeitos dos fármacos , Monoaminas Biogênicas/metabolismo , Corpo Estriado/metabolismo , Depressão/metabolismo , Dopamina/química , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Relação Dose-Resposta a Droga , Eugenol/administração & dosagem , Eugenol/efeitos adversos , Eugenol/antagonistas & inibidores , Eugenol/uso terapêutico , Comportamento Exploratório/efeitos dos fármacos , Lignanas/administração & dosagem , Lignanas/efeitos adversos , Lignanas/antagonistas & inibidores , Masculino , Camundongos , Neurônios/metabolismo , Norepinefrina/agonistas , Norepinefrina/metabolismo , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/metabolismo , Serotonina/química , Serotonina/metabolismo , Regulação para Cima/efeitos dos fármacos
4.
Phytomedicine ; 19(12): 1101-7, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22770641

RESUMO

Depression could hardly get a satisfactory effect from the currently available antidepressants. To get a more effective treatment, antidepressant effect and monoaminergic mechanism of Fructus Aurantii (FRA) in the rat forced swimming test (FST) and open field test (OFT), and its prokinetics were examined. FST and OFT were respectively used to evaluate the antidepressant effect and locomotor activity of FRA. We observed the effects of monoamine receptor antagonists on FRA-induced antidepressant effect in rat. The effects of FRA on intestinal transit, gastric emptying and in vitro jejunum contractile activity were assessed. FRA decreased significantly the immobility time (32.6±8.5, 30.3±5.2 vs 56.4±9.4, all p<0.01) in FST, dose-dependent increased the locomotor activity (102±17.5, 120±18.5 vs 89±9.8, p<0.05 or 0.01), significantly accelerated gastric emptying (GE: 48.1±6.3, 39.5±5.7 vs 19.5±3.8, p<0.01) and intestinal transit (IT: 67.3±9.1, 64.2±6.3 vs 49.1±8.2, p<0.01) of the semi-liquid meal, compared with vehicle. And FRA (1 µM, 10 µM) significantly increased the mean amplitude (0.24±0.021 and 0.281±0.015) of contraction in jejunum of rat compared with vehicle (0.149±0.011) in vitro. FRA (10 µM) could induce a largest amplitude (0.281±0.015) of contraction in jejunum. The anti-immobility effect of FRA in FST was prevented by pre-treatment of rat with p-chlorophenylalanine methyl ester, WAY100635, ketanserin, haloperidol, SCH233390, sulpiride, yohimbine, but not prazosin. FRA could simultaneously induce prokinetics and antidepressant effect, deserves further to investigate.


Assuntos
Antidepressivos/uso terapêutico , Citrus , Depressão/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Trânsito Gastrointestinal/efeitos dos fármacos , Neurotransmissores/uso terapêutico , Fitoterapia , Animais , Antidepressivos/farmacologia , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Frutas , Esvaziamento Gástrico/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Jejuno/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Neurotransmissores/farmacologia , Ratos , Ratos Sprague-Dawley , Natação
5.
Neurobiol Dis ; 37(3): 641-55, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19969082

RESUMO

The pathophysiological neural mechanism underlying the depressogenic and anxiogenic effects of chronic adolescent cannabinoid use may be linked to perturbations in monoaminergic neurotransmission. We tested this hypothesis by administering the CB(1) receptor agonist WIN55,212-2, once daily for 20 days to adolescent and adult rats, subsequently subjecting them to tests for emotional reactivity paralleled by the in vivo extracellular recordings of serotonergic and noradrenergic neurons. Chronic adolescent exposure but not adult exposure to low (0.2 mg/kg) and high (1.0 mg/kg) doses led to depression-like behaviour in the forced swim and sucrose preference test, while the high dose also induced anxiety-like consequences in the novelty-suppressed feeding test. Electrophysiological recordings revealed both doses to have attenuated serotonergic activity, while the high dose also led to a hyperactivity of noradrenergic neurons only after adolescent exposure. These suggest that long-term exposure to cannabinoids during adolescence induces anxiety-like and depression-like behaviours in adulthood and that this may be instigated by serotonergic hypoactivity and noradrenergic hyperactivity.


Assuntos
Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Encéfalo/efeitos dos fármacos , Canabinoides/toxicidade , Abuso de Maconha/fisiopatologia , Transtornos Mentais/induzido quimicamente , Fatores Etários , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Transtornos de Ansiedade/induzido quimicamente , Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Benzoxazinas/toxicidade , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Bloqueadores dos Canais de Cálcio/toxicidade , Transtorno Depressivo/induzido quimicamente , Transtorno Depressivo/metabolismo , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Emoções/efeitos dos fármacos , Emoções/fisiologia , Masculino , Abuso de Maconha/metabolismo , Abuso de Maconha/psicologia , Transtornos Mentais/metabolismo , Morfolinas/toxicidade , Naftalenos/toxicidade , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Tempo
6.
Prog Neuropsychopharmacol Biol Psychiatry ; 33(3): 530-40, 2009 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-19439241

RESUMO

Ascorbic acid is highly concentrated in the brain, being considered as a neuromodulator. This study investigated the effect of ascorbic acid in the tail suspension test (TST) and in the forced swimming test (FST) in mice and the contribution of the monoaminergic system to its antidepressant-like effect. Moreover, the effects of fluoxetine, imipramine and bupropion in combination with ascorbic acid in the TST were investigated. Ascorbic acid (0.1-10 mg/kg, i.p., 1-10 mg/kg p.o. or 0.1 nmol/mice i.c.v.) produced an antidepressant-like effect in the TST, but not in the FST, without altering the locomotor activity. The effect of ascorbic acid (0.1 mg/kg, i.p.) in the TST was prevented by i.p. pre-treatment with NAN-190 (0.5 mg/kg), ketanserin (5 mg/kg), MDL72222 (0.1 mg/kg), prazosin (62.5 microg/kg), yohimbine (1 mg/kg), propranolol (2 mg/kg), haloperidol (0.2 mg/kg), sulpiride (50 mg/kg), but not with SCH23390 (0.05 mg/kg, s.c.). Additionally, ascorbic acid (1 mg/kg, p.o.) potentiated the effect of subeffective doses (p.o. route) of fluoxetine (1 mg/kg), imipramine (0.1 mg/kg), or bupropion (1 mg/kg) in the TST. The combined treatment of ascorbic acid with antidepressants produced no alteration in the locomotion in the open-field test. In conclusion, our results show that administration of ascorbic acid produces an antidepressant-like effect in TST, which is dependent on its interaction with the monoaminergic system. Moreover, ascorbic acid caused a synergistic antidepressant-like effect with conventional antidepressants. Therefore, the present findings warrant further studies to evaluate the therapeutical relevance of ascorbic acid for the treatment of depression and as a co-adjuvant treatment with antidepressants.


Assuntos
Antidepressivos/uso terapêutico , Ácido Ascórbico/uso terapêutico , Monoaminas Biogênicas/metabolismo , Depressão/tratamento farmacológico , Transmissão Sináptica/efeitos dos fármacos , Análise de Variância , Animais , Antidepressivos/farmacologia , Ácido Ascórbico/farmacologia , Comportamento Animal/efeitos dos fármacos , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Interações Medicamentosas , Feminino , Elevação dos Membros Posteriores/métodos , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Neurotransmissores/farmacologia , Natação , Transmissão Sináptica/fisiologia
7.
Arch Neurol ; 65(5): 577-83, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18474731

RESUMO

OBJECTIVE: To assess the safety and efficacy of tesofensine, a triple monoamine reuptake inhibitor, in patients with advanced Parkinson disease (PD). DESIGN: A pilot phase 2, randomized, double-blind, placebo-controlled, parallel-group trial. The study occurred in hospital-based outpatient clinics and in clinical trial units. Patients with advanced PD and levodopa-related motor fluctuations were enrolled. Tesofensine (0.125, 0.25, 0.5, or 1 mg) or placebo tablets were administered once daily for 14 weeks. MAIN OUTCOME MEASURES: Coprimary end points were the changes from baseline in Unified Parkinson Disease Rating Scale (UPDRS) subscale II (activities of daily living) plus subscale III (motor function) total score and in percentage of waking hours spent in "off" time noted in self-scoring diaries. Secondary end points were safety, pharmacokinetics, responder analysis (> or =20% reduction in UPDRS score and in off time), and changes in percentage of waking hours spent in "on" time with and without troublesome dyskinesia. RESULTS: The adjusted mean differences (relative to placebo) were -4.7 points in UPDRS subscale II plus subscale III total score (P =.005) with tesofensine, 0.5 mg, and -7.1% in off time (-68 minutes, P =.02) with tesofensine, 0.25 mg. Other dosages did not induce statistically significant effects. The plasma concentration increased with the dosage, but no clear dose-response relationship was observed. Gastrointestinal tract and neuropsychiatric adverse events were more frequent with tesofensine than with placebo, especially at the higher dosages. CONCLUSIONS: Patients with PD in advanced stages showed modest improvements in UPDRS subscale II plus subscale III total score and in off time when treated with tesofensine, but a dose-response relationship could not be established for efficacy, while adverse drug reactions tended to be more frequent at higher dosages. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00148512.


Assuntos
Monoaminas Biogênicas/agonistas , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Inibidores da Captação de Neurotransmissores/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/sangue , Progressão da Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Masculino , Transtornos Mentais/induzido quimicamente , Pessoa de Meia-Idade , Inibidores da Captação de Neurotransmissores/efeitos adversos , Inibidores da Captação de Neurotransmissores/sangue , Projetos Piloto , Placebos , Resultado do Tratamento
8.
Behav Brain Res ; 189(1): 32-40, 2008 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-18243356

RESUMO

Self-injurious behaviour (SIB) is exhibited by individuals with a broad variety of developmental disorders and genetic abnormalities, including autism and Lesch-Nyhan, Prader-Willi and Rett syndromes. Most research has focused on environmental factors that reinforce SIB, and less is known about the biological basis of this behaviour disorder. However, animal models have been developed to study the neurochemical pathology that underlies SIB. In one model, rats exhibit self-biting after repeated daily administration of moderately high doses of pemoline (100-200mg/kg). Dopaminergic and glutamatergic neurotransmission have been implicated in this model. Accordingly, we investigated the role of glutamatergic neurotransmission in pemoline-induced SIB, using the N-methyl-d-aspartate (NMDA) receptor antagonists MK-801 and memantine. MK-801 is a high affinity antagonist which blocks glutamate-mediated neuroplasticity and behavioural sensitization to other psychostimulants. It lessened the incidence of SIB, the time spent self-injuring, and the area of tissue damage in the pemoline model. Memantine, on the other hand, is a low affinity antagonist which does not disrupt glutamate-mediated neuroplasticity, and it had little if any effect on any measure of pemoline-induced SIB. These results suggest that repeated pemoline administration induces glutamate-mediated neuroplastic changes that lead to the eventual expression of SIB. Further investigation of these changes may reveal specific neurochemical factors that contribute to SIB in this animal model of self-injury.


Assuntos
Comportamento Animal/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Memantina/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Comportamento Autodestrutivo/metabolismo , Animais , Monoaminas Biogênicas/agonistas , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Inibidores da Captação de Neurotransmissores , Pemolina , Ratos , Ratos Long-Evans , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Comportamento Autodestrutivo/induzido quimicamente
9.
Neurosci Behav Physiol ; 38(2): 115-8, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18197375

RESUMO

Microinjections of serotonin and glutamic acid into the globus pallidus in conditions of free selection between a light and a dark chamber showed these substances to have antiaversive activity in rats in the "threatening situation" test but not in the "illuminated area" test. Local administration of dopamine and GABA into this basal ganglia formation had no effect on the mechanisms of voluntary movement but countered anxiety states in both behavioral models. These results provide evidence that the neurotransmitter systems of the dorsal pallidum have different degrees of involvement in the operative control of behavior when the modality of the aversive stimulus changes.


Assuntos
Aminoácidos/farmacologia , Ansiedade/prevenção & controle , Ansiedade/psicologia , Monoaminas Biogênicas/farmacologia , Globo Pálido/fisiologia , Aminoácidos/agonistas , Aminoácidos/antagonistas & inibidores , Animais , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Condicionamento Operante/efeitos dos fármacos , Globo Pálido/efeitos dos fármacos , Ácido Glutâmico/administração & dosagem , Ácido Glutâmico/farmacologia , Masculino , Microinjeções , Motivação , Atividade Motora/efeitos dos fármacos , Ratos , Reforço Psicológico , Serotonina/farmacologia , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/farmacologia
10.
Curr Opin Neurol ; 19(6): 607-12, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17102701

RESUMO

PURPOSE OF REVIEW: Problems relating to impulsivity, attention, and working memory occur in many neuropsychiatric disorders and represent important targets for pharmacological intervention. The purpose of this article is to review recent neuropharmacological manipulation studies in humans relating to these domains. RECENT FINDINGS: Serotonin manipulations in healthy volunteers did not affect response inhibition, a cognitive function implicated in impulsive symptoms of attention deficit hyperactivity disorder, trichotillomania, and substance abuse. Serotonin manipulations did affect performance on cognitive tests involving emotionally salient rewards and feedback, suggesting involvement of this neurochemical in affective aspects of impulsivity. Attentional deficits in attention deficit hyperactivity disorder and visuospatial neglect were ameliorated by noradrenergic drugs. Noradrenergic beta-blockade suppressed the encoding of emotionally arousing unpleasant stimuli and reduced amygdala activation in healthy volunteers, with potential implications for posttraumatic stress disorder. Dopaminergic manipulations affected aspects of working memory in healthy volunteers and in patients with Parkinson's disease, with evidence for bidirectional effects depending on baseline performance. SUMMARY: Recent findings raise exciting prospects for modulating impulsivity, attention, and working memory in a variety of neuropsychiatric disorders. Future studies should use computerized cognitive assessment, measures of functional genetic polymorphisms, and neuroimaging techniques, in order to further elucidate the neurochemical substrates of cognition and optimize treatment approaches.


Assuntos
Monoaminas Biogênicas/metabolismo , Encéfalo/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Neurotransmissores/metabolismo , Psicotrópicos/farmacologia , Atenção/efeitos dos fármacos , Atenção/fisiologia , Monoaminas Biogênicas/agonistas , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/metabolismo , Humanos , Comportamento Impulsivo/tratamento farmacológico , Comportamento Impulsivo/metabolismo , Comportamento Impulsivo/fisiopatologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Neurotransmissores/agonistas , Psicotrópicos/uso terapêutico
11.
Curr Opin Neurol ; 19(6): 613-8, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17102702

RESUMO

PURPOSE OF REVIEW: Recent work has revealed the impact of deficits of attention on patients with neurological disorders. Here we discuss therapeutic interventions that have been used across a range of conditions, highlighting common themes both in the nature of the attention deficits and the strategies employed to treat them. RECENT FINDINGS: Cholinesterase inhibitors improve attention, as well as memory, in several conditions including cortical Lewy body disease, Parkinson's disease dementia, traumatic brain injury and Alzheimer's disease. Recent studies suggest that cholinergic stimulation may boost attention further if more specific nicotinic cholinergic agonists are used, or if cholinesterase inhibitors are combined with other agents. Monoaminergic drugs have been shown to improve attention in traumatic brain injury, attention-deficit hyperactivity disorder and hemispatial neglect following right-hemisphere stroke. New compounds targeting other neurotransmitter systems are currently being tested, while several types of behavioural intervention have shown promise, particularly in stroke patients. SUMMARY: Pharmacological and behavioural interventions can improve attention in neurological patients. In the future, optimum therapy may depend on careful delineation of the components of attention that are impaired as well as assessment of the potential for surviving brain regions to compensate for attention deficits.


Assuntos
Atenção/efeitos dos fármacos , Encefalopatias/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Transtornos Neurocognitivos/tratamento farmacológico , Atenção/fisiologia , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/metabolismo , Encéfalo/fisiopatologia , Dano Encefálico Crônico/tratamento farmacológico , Dano Encefálico Crônico/fisiopatologia , Dano Encefálico Crônico/psicologia , Encefalopatias/fisiopatologia , Encefalopatias/psicologia , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Agonistas Colinérgicos/farmacologia , Humanos , Transtornos Neurocognitivos/fisiopatologia , Transtornos Neurocognitivos/psicologia , Neurofarmacologia/tendências
12.
Nervenarzt ; 77(4): 403-15, 2006 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-16273340

RESUMO

Aphasia is one of the most frequent and disabling consequences of stroke. Poor spontaneous recovery and the limited success of conventional speech therapy bring up the question of how current treatment approaches can be improved. Besides increasing training frequency-with daily sessions lasting several hours and high repetition rates of language materials ("massed training")-adjuvant drug therapy may help to increase therapy efficacy. In this article, we illuminate the potential of monoaminergic (bromocriptine, levodopa, d-amphetamine) and cholinergic (donepezil) substances for treating aphasia. For a final evaluation of combined massed training and adjuvant pharmacotherapy, randomized, placebo-controlled (multicenter) clinical trials with sufficient numbers of patients are needed. Furthermore, results of experimental animal studies of functional recovery in brain damage raise hopes that neurotrophic factors or stem cells might find a place in recovery from aphasia in the intermediate future.


Assuntos
Afasia/tratamento farmacológico , Monoaminas Biogênicas/agonistas , Colinérgicos/administração & dosagem , Infarto da Artéria Cerebral Anterior/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Nootrópicos/administração & dosagem , Afasia/diagnóstico , Monoaminas Biogênicas/uso terapêutico , Encéfalo/efeitos dos fármacos , Terapia Combinada , Humanos , Infarto da Artéria Cerebral Anterior/diagnóstico , Infarto da Artéria Cerebral Média/diagnóstico , Terapia da Linguagem , Potenciação de Longa Duração/efeitos dos fármacos , Fatores de Crescimento Neural/administração & dosagem , Transplante de Células-Tronco
13.
Neuropharmacology ; 48(1): 62-71, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15617728

RESUMO

This study examines the effect of long-term elevation of brain monoamine levels on receptor/G-protein coupling by chronic administration of a highly potent tropane analog, WF-23 (2beta-propanoyl-3beta-(2-naphthyl) tropane). WF-23 blocks dopamine, serotonin and norepinephrine transporters with high affinity in vitro, and blocks transporters for at least two days following a single in vivo administration. Rats were chronically treated for 15 days with 1mg/kg WF-23, injected i.p. every two days. Receptor activation of G-proteins was determined by [35S]GTPgammaS autoradiography in brain sections for D2, 5-HT1A and alpha2-adrenergic receptors, as well as mu opioid receptors as a non-monoamine receptor control. Chronic treatment with WF-23 produced significant reductions in D2, 5-HT1A, and alpha2-adrenergic receptor-stimulated [35S]GTPgammaS binding in caudate/putamen, hippocampus and amygdala, respectively. There were no effects of WF-23 treatment on mu opioid-stimulated [35S]GTPgammaS binding. Additionally, there was no effect of WF-23 treatment on D2 receptor binding, as determined by [3H]spiperone autoradiography. These data show that chronic blockade of monoamine transporters produces specific uncoupling of receptors and G-proteins in specific brain regions in the absence of receptor downregulation.


Assuntos
Apomorfina/análogos & derivados , Monoaminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Cocaína/análogos & derivados , Cocaína/farmacologia , Moduladores de Transporte de Membrana , Proteínas de Membrana Transportadoras/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Animais , Apomorfina/farmacologia , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Encéfalo/anatomia & histologia , Cocaína/química , Antagonistas de Dopamina/farmacocinética , Esquema de Medicação , Interações Medicamentosas , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Guanosina 5'-O-(3-Tiotrifosfato)/farmacocinética , Isótopos/farmacocinética , Masculino , Ligação Proteica/efeitos dos fármacos , Ensaio Radioligante/métodos , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Espiperona/farmacocinética , Tempo
14.
Artigo em Inglês | MEDLINE | ID: mdl-15160282

RESUMO

The monoamines, dopamine, epinephrine, histamine, norepinephrine, octopamine, serotonin and tyramine serve many functions in animals. Many different venoms have evolved to manipulate monoaminergic systems via a variety of cellular mechanisms, for both offensive and defensive purposes. One common function of monoamines present in venoms is to produce pain. Some monoamines in venoms cause immobilizing hyperexcitation which precedes venom-induced paralysis or hypokinesia. A common function of venom components that affect monoaminergic systems is to facilitate distribution of other venom components by causing vasodilation at the site of injection or by increasing heart rate. Venoms of some scorpions, spiders, fish and jellyfish contain adrenergic agonists or cause massive release of catecholamines with serious effects on the cardiovascular system, including increased heart rate. Other venom components act as agonists, antagonists or modulators at monoaminergic receptors, or affect release, reuptake or synthesis of monoamines. Most arthropod venoms have insect targets, yet, little attention has been paid to possible effects of these venoms on monoaminergic systems in insects. Further research into this area may reveal novel effects of venom components on monoaminergic systems at the cellular, systems and behavioral levels.


Assuntos
Monoaminas Biogênicas/metabolismo , Peçonhas/metabolismo , Animais , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Histamina/metabolismo , Humanos , Especificidade da Espécie , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Peçonhas/farmacologia
15.
J Pharmacol Exp Ther ; 308(1): 111-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14569055

RESUMO

Monoaminergic drugs can modify opioid withdrawal in nonhumans, and cocaine is reported to attenuate opioid withdrawal in humans. Drug discrimination was used to examine whether s.c. cocaine or other indirect-acting monoamine agonists attenuate morphine (3.2 mg/kg/day) withdrawal induced by naltrexone and by 27 h of morphine deprivation. Naltrexone-precipitated withdrawal was attenuated not only by morphine but also by cocaine, amphetamine, and imipramine. However, reversal of naltrexone-precipitated withdrawal was greater for morphine than for any of the indirect-acting monoamine agonists. Attenuation of the naltrexone discriminative stimulus by indirect-acting monoamine agonists was pharmacologically selective insofar as drugs lacking affinity for monoamine transporters (ketamine and triazolam) were without effect. Twenty-seven hours of morphine deprivation occasioned naltrexone-lever responding and decreased response rate, and both effects were reversed by morphine, cocaine, and amphetamine and not by imipramine, desipramine, ketamine, and triazolam. Thus, indirect-acting monoamine agonists attenuate some (e.g., discriminative) aspects of naltrexone-precipitated withdrawal, whereas only indirect-acting agonists with high affinity for dopamine transporters attenuate deprivation-induced withdrawal. These results suggest that dopamine is differentially involved in naltrexone- and deprivation-induced withdrawal and support the notion that opioid-dependent individuals use stimulants, in part, to attenuate withdrawal.


Assuntos
Cocaína/uso terapêutico , Aprendizagem por Discriminação/efeitos dos fármacos , Dopaminérgicos/uso terapêutico , Morfina/efeitos adversos , Naltrexona/farmacologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Anfetamina/uso terapêutico , Animais , Monoaminas Biogênicas/agonistas , Modelos Animais de Doenças , Inibidores da Captação de Dopamina/uso terapêutico , Interações Medicamentosas , Imipramina/uso terapêutico , Macaca mulatta , Dependência de Morfina , Entorpecentes/efeitos adversos
16.
Cell Mol Neurobiol ; 23(3): 419-30, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12825836

RESUMO

1. AMPA receptor potentiators (ARPs) exhibit antidepressant-like activity in preclinical tests (for example, the forced swim test) that are highly predictive of efficacy in humans. Unlike most currently used antidepressants, ARPs do not elevate extracellular levels of biogenic amines (e.g., 5HT, NE) in prefrontal cortex at doses that are active in the forced swim test. 2. The present series of experiments examined the effects of combining the ARP, LY 392098, with biogenic amine-based antidepressants in the forced swim test. Male, NIH Swiss mice were placed in a cylinder of water and observed for attempted escape behaviors and immobility. 3. LY 392098 dose-dependently decreased immobility as did a range of classical antidepressants. At doses of LY 392098 below those that decreased immobility, this compound significantly increased the potency with which fluoxetine and citalopram (SSRI antidepressants), imipramine (tricyclic antidepressant), duoxetine (norepinephrine/serotonin uptake blocker), nisoxetine (norepinephrine uptake inhibitor), and rolipram (PDE4 inhibitor) decreased immobility in the forced swim test with potency shifts upward of 5-fold (fluoxetine, imipramine, and rolipram). Likewise, ineffective doses of the traditional antidepressants potentiated the effects LY 392098 with shifts in the dose-effect functions that were 10-fold or more for citalopram, fluoxetine, imipramine, and duloxetine. 4. Combined with other evidence for a role of AMPA receptors in the efficacy of antidepressants, the current data suggest that the addition of an ARP may augment the activity and perhaps the onset of the therapeutic effects of biogenic amine and second messenger-based antidepressants.


Assuntos
Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Transtorno Depressivo/tratamento farmacológico , Agonistas de Aminoácidos Excitatórios/farmacologia , Neurônios/efeitos dos fármacos , Receptores de AMPA/efeitos dos fármacos , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Animais , Antidepressivos/uso terapêutico , Antidepressivos Tricíclicos/farmacologia , Monoaminas Biogênicas/agonistas , Encéfalo/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Agonistas de Aminoácidos Excitatórios/uso terapêutico , Masculino , Camundongos , Neurônios/metabolismo , Receptores de AMPA/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico
17.
CNS Drugs ; 17(8): 539-62, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12775192

RESUMO

Extracts of Hypericum perforatum L. (St John's wort) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the active antidepressant compounds in the extract. From a phytochemical point of view, St John's wort is one of the best-investigated medicinal plants. A series of bioactive compounds has been detected in the crude material, namely flavonol derivatives, biflavones, proanthocyanidines, xanthones, phloroglucinols and naphthodianthrones. Although St John's wort has been subjected to extensive scientific studies in the last decade, there are still many open questions about its pharmacology and mechanism of action. Initial biochemical studies reported that St John's wort is only a weak inhibitor of monoamine oxidase-A and -B activity but that it inhibits the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. However, other in vitro binding assays carried out using St John's wort extract demonstrated significant affinity for adenosine, GABA(A), GABA(B) and glutamate receptors. In vivo St John's wort extract leads to a downregulation of beta-adrenergic receptors and an upregulation of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression, St John's wort extracts induced a significant reduction of immobility. In other experimental models of depression, including acute and chronic forms of escape deficit induced by stressors, St John's wort extract was shown to protect rats from the consequences of unavoidable stress. Recent neuroendocrine studies suggest that St John's wort is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function. With regard to the antidepressant effects of St John's wort extract, many of the pharmacological activities appear to be attributable to the naphthodianthrone hypericin, the phloroglucinol derivative hyperforin and several flavonoids. This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John's wort and its active constituents with a large body of existing literature.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Hypericum/química , Fitoterapia , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Medicina do Comportamento , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Monoaminas Biogênicas/metabolismo , Modelos Animais de Doenças , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Receptores de Neurotransmissores/efeitos dos fármacos , Receptores de Neurotransmissores/fisiologia
18.
Ross Fiziol Zh Im I M Sechenova ; 87(9): 1217-26, 2001 Sep.
Artigo em Russo | MEDLINE | ID: mdl-11763535
19.
Psychopharmacology (Berl) ; 113(1): 76-82, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-7862832

RESUMO

Narcolepsy is currently treated with anti-depressants to control REM-related symptoms such as cataplexy and with amphetamine-like stimulants for the management of sleepiness. Both stimulant and antidepressant drugs presynaptically enhance monoaminergic transmission but both classes of compounds lack pharmacological specificity. In order to determine which monoamine is selectively involved in the therapeutic effect of these compounds, we examined the effects of selective monoamine uptake inhibitors and release enhancers on cataplexy using a canine model of the human disorder. A total of 14 compounds acting on the adrenergic (desipramine, nisoxetine, nortriptyline, tomoxetine, viloxazine), serotoninergic (fenfluramine, fluoxetine, indalpine, paroxetine, zimelidine) and dopaminergic (amfonelic acid, amineptine, bupropion, GBR 12909) systems were tested. Some additional compounds interesting clinically but with less pharmacological selectivity, i.e., cocaine, dextroamphetamine, methylphenidate, nomifensine and pemoline, were also included in the study. All compounds affecting noradrenergic transmission completely suppressed canine cataplexy at low doses in all dogs tested, whereas compounds which predominantly modified serotoninergic and dopaminergic transmission were either inactive or partially active at high doses. Our results demonstrate the preferential involvement of adrenergic systems in the control of cataplexy and, presumably, REM sleep atonia. Our findings also demonstrate that canine narcolepsy is a useful tool in assessing the pharmacological specificity of antidepressant drugs.


Assuntos
Monoaminas Biogênicas/agonistas , Cataplexia/fisiopatologia , Inibidores da Captação de Neurotransmissores/farmacologia , Sistema Nervoso Parassimpático/fisiopatologia , Adrenérgicos/farmacologia , Anfetaminas/farmacologia , Animais , Monoaminas Biogênicas/metabolismo , Cães , Dopaminérgicos/farmacologia , Norepinefrina/fisiologia , Receptores Pré-Sinápticos/efeitos dos fármacos , Serotoninérgicos/farmacologia , Transmissão Sináptica/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...