RESUMO
The effects of Hypericum perforatum, a plant with antidepressant action, were evaluated in models of abnormal movements in rats, brought about by administration of fluphenazine or reserpine. The number of vacuous chewing movements (VCMs) and locomotor activity (the number of crossings and rears in the open field test) were measured. In experiment 1, rats received a single administration of fluphenazine enanthate (25 mg/kg, intramuscular) and/or daily treatment with H. perforatum (300 mg/kg, in place of drinking water) for 7 days. Fluphenazine increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the locomotor activity. In experiment 2, rats received reserpine every 2 days for 6 days (0.5 mg/kg, subcutaneous) and/or H. perforatum (300 mg/kg, in place of drinking water) daily for 16 days beginning 10 days before the first administration of reserpine. Reserpine treatment increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the number of rears but did prevent the effect of reserpine on the number of crossings. In conclusion, H. perforatum failed to protect against orofacial movements induced by fluphenazine or reserpine in rats.
Assuntos
Hypericum/química , Transtornos dos Movimentos/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , Flufenazina/análogos & derivados , Flufenazina/toxicidade , Masculino , Mastigação/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Reserpina/toxicidadeRESUMO
RATIONALE: Chronic treatment with neuroleptics causes, as a side effect, tardive dyskinesia in humans; however, the mechanisms involved in its pathophysiology remain unclear. OBJECTIVES: The purpose of this study was to examine the effects of diphenyl diselenide, an organoselenium compound with antioxidant properties, in an animal model of vacuous chewing movements (VCMs) induced by long-term treatment with fluphenazine. RESULTS: Adult male rats were treated during 24 weeks with fluphenazine (25 mg/kg, intramuscularly [i.m.], once every 21 days) and diphenyl diselenide (1 mg/kg, subcutaneously, three times a week). VCMs and body weight gain were quantified every 3 weeks. The fluphenazine treatment produced VCMs in the majority of the treated rats (87% after 24 weeks). Concomitant treatment with diphenyl diselenide decreased the prevalence of VCMs to 50%. Additionally, we separated the rats that developed or did not develop VCMs. We did not find any statistical differences among the groups when oxidative stress parameters were evaluated. Chronic fluphenazine treatment significantly decreased [(3)H]-dopamine uptake. Concomitant treatment with diphenyl diselenide was not able to prevent this decrease in those rats that developed VCMs. CONCLUSIONS: Our data suggest that the reduction in dopamine transport can be a possible mechanism related to the maintenance of VCMs in rats. Moreover, diphenyl diselenide seems to be a promising pharmacological agent in the reduction in the prevalence of VCMs in rats.
Assuntos
Antioxidantes/farmacologia , Derivados de Benzeno/farmacologia , Antagonistas de Dopamina/efeitos adversos , Mastigação/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Animais , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Dopamina/metabolismo , Antagonistas de Dopamina/administração & dosagem , Relação Dose-Resposta a Droga , Discinesia Induzida por Medicamentos/tratamento farmacológico , Discinesia Induzida por Medicamentos/fisiopatologia , Flufenazina/administração & dosagem , Flufenazina/efeitos adversos , Flufenazina/análogos & derivados , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
BACKGROUND: Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken. METHODS: In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks. RESULTS: For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression. CONCLUSION: Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.
Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Flufenazina/análogos & derivados , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adolescente , Adulto , Assistência Ambulatorial , Antipsicóticos/efeitos adversos , Transtornos de Ansiedade/induzido quimicamente , Transtornos de Ansiedade/diagnóstico , Doenças dos Gânglios da Base/diagnóstico , Doenças dos Gânglios da Base/etiologia , Doenças dos Gânglios da Base/prevenção & controle , Benzotropina/análogos & derivados , Benzotropina/uso terapêutico , Transtorno Depressivo/induzido quimicamente , Transtorno Depressivo/diagnóstico , Desipramina/uso terapêutico , Diagnóstico Diferencial , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Flufenazina/uso terapêutico , Glicopirrolato/uso terapêutico , Humanos , Carbonato de Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Placebos , Escalas de Graduação Psiquiátrica , Fatores SexuaisRESUMO
Two hundred and thirty-two psychiatric Outpatients on depot fluphenazine decanoate for more than six months were examined for Tardive Dyskinesia (TD), using the AIMS rating scale, and the prevalence rates of TD at different criteria of severity were assessed. The prevalence rates ranged from 7% for patients with severe TD to 45% for patients with any degree of TD. The sex distribution of patients with TD showed no bias but the female patients were significantly older than the male patients. Increases in prevalence rates of TD were associated with the combination of an anticholinergic anti-Parkinsonian drug with the depot neuroleptic, and with the concomitant use of an oral neuroleptic with the depot preparation. Implications of these findings for the long-term management of schizophrenia are discussed.
Assuntos
Assistência Ambulatorial , Antipsicóticos/efeitos adversos , Discinesia Induzida por Medicamentos/etiologia , Transtornos Mentais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Preparações de Ação Retardada , Feminino , Flufenazina/efeitos adversos , Flufenazina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológicoRESUMO
Two hundred and thirty-two psychiatric Outpatients on depor fluphenazine decanoate for more than six months were examined for Tardive Dyskinesia (TD), using the AIMS rating scale, and the prevalence rates of TD at different criteria of severity were asssessed. The prevalence rates ranged from 7% for patients with asevere TD to 45% for patients with any degree of TD. The sex distribution of patients with TD showed no bias but the female patients were significantly older than the male patients. Increases in prevalence rats of TD were associated with the combination of an anticholinergic anti-Parkinsonian drug with the depot neuroleptic, and with the concomitant use of an oral neuroleptic with the depot preparation. Implications of these finding for the long-term management of schizopherinia are discussed