Sleep pharmacology of typical and atypical ligands of benzodiazepine receptors.

The effects of several benzodiazepine and non-benzodiazepine ligands of benzodiazepine receptors have been investigated in sleep of normal young adults. The spectrum of activity of each compound has been characterized using a number of sleep variables in addition to the standard sleep stages. These substances affect all the principal components of sleep, that is the sleep-wake balance, paradoxical sleep, orthodox sleep and the EEG waveforms in the different sleep stages. Some, but not all, modifications induced by flunitrazepam are antagonized by flumazenil and they recover with various time constants after a single administration of the drug. The results of these experiments indicate a heterogeneity in the mechanism of action of benzodiazepine and non-benzodiazepine ligands of benzodiazepine receptors, because they affect differently the various components of sleep. It is not necessary to invoke a heterogeneity of the central benzodiazepine receptors (the BZ1-BZ2 theory) in order to account for these differences, but they can be explained by the concept of spare receptors.