Zolpidem is an imidazopyridine which binds specifically to the omega 1 receptor. Zolpidem demonstrated potent hypnotic activity at a dose of 10 mg. Pharmacodynamics and pharmacokinetics of zolpidem were studied after daytime administration in a randomised, double-blind, placebo-controlled, cross-over trial. Single doses of zolpidem (10 mg IV as a 3-min infusion and 20 mg orally) and placebo were firstly tested in 12 healthy young male volunteers. Two other doses (5 mg IV and orally) were then evaluated in 6 out of these 12 subjects. EEG (4 leads = Fp2-T4, Fp1-T3, T4-02 and T3-01), and Stanford Sleepiness Scale (SSS) were measured up to 5 h postdosing. Blood samples were also collected up to 24 h. The time course of the hypnotic activity of zolpidem, assessed by the score obtained on SSS, showed a similar profile whatever the route or the dose administered: slightly earlier onset after IV but sedative scores were reached at 30 min and the effect peaked between 1 and 1.5 h and lasted 4 h in both conditions. The EEG profile of zolpidem was characterised by a decrease of alpha activity and an increase in delta and in beta activity. The effect on beta activity was marked within the first hour and then disappeared. The time course of delta and alpha activities indicated a rapid onset (10 min after IV, 30 min after oral route) and a duration of 3-4 h. The amplitude of these relative EEG changes and their duration were independent of the route of administration and the dose administered. AUC and Cmax increased proportionally to the administered dose and elimination half life (2h), clearance and volume of distribution did not change according to the dose or the route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell genesis in the subgranular zone of the dentate gyrus of 2-month-old rabbits has been investigated. After incorporation of tritiated thymidine, electron microscopic autoradiography allowed description of the ultrastructure of the cells labelled and the progressive transformation of these cells into granular neurons to be followed. Quantitative evaluation of the time course of this transformation has been performed by light microscope autoradiography using 1-µm sections. Precursor cells, labelled initially with ³H-thymidine, were transformed after 5 days into early neuroblasts, these cells in turn giving rise to neurons some 8 days later. At the latest time period examined (42 days), 80% of the labelled cells were neurons; more than 10% remained as precursor cells. It is suspected that the latter may behave as reserve cells. Small numbers of glial cells, astrocytes, and microglia, scattered throughout the talus of the dentate gyrus and the molecular layer, were found labelled, and it is possible that they arise from a different precursor pool. It is concluded that the subgranular zone functions as a secondary matrix for granule neurons of the dentate gyrus in young rabbits. These late-forming and apparently synaptically uncommitted neurons may be recruited during the development and refinement of postnatal behavioral substrates, by one or other of the dominant afferent systems.

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