RESUMO
We have assessed the effect of midazolam on sleep in a model of transient insomnia in healthy adults using polysomnographic recordings. The subjects were randomly assigned to one of three treatment groups (placebo or midazolam 7.5 or 15 mg) and spent a single night in the sleep laboratory. Midazolam or placebo were given double-blind immediately before turning off the lights. Midazolam 15 mg was effective in inducing sleep, while 7.5 mg and 15 mg produced improvement in the maintenance of sleep. Subjectively, sleep latency and the number of awakenings were reduced dose-dependently. Midazolam did not impair psychomotor performance on the morning after administration.
Assuntos
Midazolam/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Midazolam/administração & dosagem , Midazolam/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Sono/efeitos dos fármacos , Sono REM/efeitos dos fármacos , Fatores de TempoRESUMO
The effects of the histamine H3 receptor agonist, (R)-alpha-methylhistamine were compared with those of the histamine H3 antagonist, thioperamide, in rats implanted with electrodes for chronic sleep recordings. (R)-alpha-Methylhistamine (1.0-4.0 micrograms) injected bilaterally into the premammillary area where histamine immunoreactive neurons have been detected increased slow wave sleep, whereas wakefulness and REM sleep were decreased. No significant effects were observed when (R)-alpha-methylhistamine (1.0-8.0 mg/kg) was administered i.p. Thioperamide (1.0-4.0 mg/kg i.p.) increased wakefulness and decreased slow wave sleep and REM sleep. Pretreatment with thioperamide (4.0 mg/kg) prevented the effects of (R)-alpha-methylhistamine (2.0 micrograms) on slow wave sleep and wakefulness. Our results further support an active role for histamine in the control of the waking state.
Assuntos
Receptores Histamínicos/efeitos dos fármacos , Sono/efeitos dos fármacos , Vigília/efeitos dos fármacos , Animais , Interações Medicamentosas , Antagonistas dos Receptores Histamínicos , Injeções Intraperitoneais , Injeções Intraventriculares , Masculino , Corpos Mamilares , Metilistaminas/antagonistas & inibidores , Metilistaminas/farmacologia , Piperidinas/farmacologia , Ratos , Ratos Endogâmicos , Receptores Histamínicos/fisiologia , Receptores Histamínicos H3RESUMO
The effects of the H1-receptor antagonist diphenhydramine and the brain-penetrating H2-receptor antagonist zolantidine were studied in rats implanted for chronic sleep recordings. Diphenhydramine (1.0-4.0 mg/kg) significantly increased slow wave sleep and decreased wakefulness. Zolantidine (0.25-8.0 mg/kg) had no significant effects on any of the sleep parameters examined. One possibility is that zolantidine did not enter the brain in sufficient concentration to produce significant changes on sleep and wakefulness. Another possibility is that blockade of H2-receptor involved parts of the brain other than those implicated in the sleep-wake cycle. The feasibility remains that H2-receptors are not involved in sleep regulation. The absence of selective, brain-penetrating H2-receptor agonists precludes a more detailed analysis of the role of this subtype of receptor in the control of sleep and wakefulness.