RESUMO
Donepezil is a cholinesterase inhibitor used for the treatment of patients with mild to moderately severe Alzheimer's disease (AD). The purpose of this study was to determine the effect of treatment with donepezil 5 mg qd on cognitive evoked potentials (EPs) of patients with AD. Although treatment with donepezil did not normalize EP latencies, treatment was associated with a significant decrease in the auditory P300 latency (mean latency pretreatment=401. 5 msec; posttreatment=392.7 msec.; P=0.04), and the visual P300 latency (mean latency pretreatment=605.7 msec; posttreatment=580.3 msec; P=0.04). Treatment with donepezil had no discernible effect on auditory or visual P300 EP amplitudes.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Indanos/uso terapêutico , Nootrópicos/uso terapêutico , Piperidinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Donepezila , Feminino , Humanos , Masculino , Período Refratário Eletrofisiológico/efeitos dos fármacosRESUMO
Adult male and female genetically seizure-prone rats were assessed for sound-induced seizures. Heterozygous control groups were compared with mild seizure (designated GEPR 3) and severe seizure animals (GEPR 9). Groups of animals were killed and crude synaptosome fractions (P2) prepared from freshly dissected cerebral cortices. Binding sites for gamma-aminobutyric acid (GABA) were assessed by [3H]-muscimol in the absence or presence of excess GABA and/or pentobarbital. Binding sites for benzodiazepines were assessed by [3H]-flunitrazepam in the presence or absence of clonazepam. Compared to controls, GEPR 3 animals had a modest increase and GEPR 9 animals a larger increase in Bmax for both high and low affinity GABA sites, with no change in Kd. Chloride-dependent, barbiturate-enhanced GABA binding (increased Bmax) was observed in all conditions and groups. Likewise benzodiazepine binding (Bmax) increased slightly in GEPR 9 animals. There were no observed changes in binding sites for a survey of biogenic amines. Seizure-prone animals appear to have compensatory denervation-like supersensitivity for their most prominent inhibitory receptor, which may or may not be linked to the seizure event.
