RESUMO
Erythrosin B is a member of a class of fluorescein dyes that are suggested to elicit hyperkinesis when ingested by susceptible children. We found that erythrosin B inhibits dopamine uptake in rat caudate synaptosomes "uncompetitively" in the 10- to 800-micromolar range. Half maximal inhibition of uptake occurred at 45 micromolar. Uncompetitive inhibition denotes a decrease in efficacy of the dopamine membrane transport mechanism with an increase in affinity of dopamine to the carrier. Erythrosin B also decreased nonsaturable binding of dopamine to the synaptosome membrane. The inhibitory action of erythrosin B on dopamine uptake is consistent with the hypothesis that erythrosin B can act as a central excitatory agent able to induce hyperkinetic behavior.
Assuntos
Núcleo Caudado/metabolismo , Dopamina/metabolismo , Eritrosina/farmacologia , Fluoresceínas/farmacologia , Sinaptossomos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Núcleo Caudado/efeitos dos fármacos , Cinética , Ratos , Sinaptossomos/efeitos dos fármacosRESUMO
A double-blind, placebo-controlled trial of gamma-vinyl gamma-aminobutyric acid (GVG) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c) pyridine-3-ol (THIP) was carried out in drug-free schizophrenic patients with tardive dyskinesia. A significant decrease in dyskinetic symptoms occurred with the administration of GVG, associated with a twofold increase in cerebrospinal fluid levels of GABA; THIP produced a more moderate, yet consistent decrease in the involuntary movements. A pathophysiologic role for gamma-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia. A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls. These data compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.
Assuntos
Encéfalo/metabolismo , Discinesia Induzida por Medicamentos/fisiopatologia , Ácido gama-Aminobutírico/fisiologia , Adulto , Aminocaproatos/farmacologia , Aminocaproatos/uso terapêutico , Encéfalo/efeitos dos fármacos , Ensaios Clínicos como Assunto , Método Duplo-Cego , Discinesia Induzida por Medicamentos/tratamento farmacológico , Discinesia Induzida por Medicamentos/metabolismo , Feminino , Humanos , Isoxazóis/farmacologia , Masculino , Pessoa de Meia-Idade , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Esquizofrenia/líquido cefalorraquidiano , Esquizofrenia/metabolismo , Vigabatrina , Ácido gama-Aminobutírico/líquido cefalorraquidiano , Ácido gama-Aminobutírico/metabolismoRESUMO
Lithium has been used successfully to enhance the effectiveness of tricyclic and other antidepressants, monoamine oxidase inhibitors, and combinations of antipsychotics and antidepressants. The safety and efficacy of adding lithium to the treatment regimen was examined in 14 elderly patients with refractory depression. Seven of the 14 had a complete recovery, and three showed a partial response. Side effects, including peripheral weakness, severe fine tremor, and neurotoxicity, necessitated the discontinuation of lithium in three patients. In two other patients with side effects, lower dosages of lithium relieved their symptoms. Lithium augmentation appears to be a promising treatment for geriatric depressed patients who are unresponsive to or cannot tolerate other standard therapies.