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[A specific domain (the omega 1 site) of the GABA(A) receptor may be implicated in the hypnotic effects of zolpidem].

Zolpidem (Stilnox) is a new hypnotic belonging to the imidazopyridine series. In animals, in contrast to the benzodiazepines which alter sleep architecture, zolpidem induces a physiological pattern of deep sleep. Zolpidem also differs from the benzodiazepines by its hypnoselective profile (its sedative effects are seen at doses much lower than those needed for anticonvulsant or myorelaxant effects). In this review, the authors analyze the hypothesis that the hypnoselective profile of zolpidem is linked to its interaction with a specific domain, the omega 1 site, of the GABAA receptor complex. This hypothesis is supported by: 1) the high selectivity of zolpidem for omega 1 as compared to omega 2 sites and its high intrinsic activity, 2) autoradiographic studies of the regional distribution of omega 1 and omega 2 sites in the human and non-human primate brains showing that omega 1 sites are located preferentially in sensorimotor cortical regions whereas omega 2 sites predominate in the limbic system and spinal cord. The selectivity of zolpidem for omega 1 sites could also account for the fact that in contrast to the benzodiazepines, this compound does not alter memory functions at hypnotic doses.