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  • Title: Degree of sedation obtained with various doses of diazepam and nitrazepam.
    Author: Grundström R, Holmberg G, Hansen T.
    Journal: Acta Pharmacol Toxicol (Copenh); 1978 Jul; 43(1):13-8. PubMed ID: 707120.
    Abstract:
    Using critical flicker fusion (CFF) determination and estimation of drowsiness in eight healthy volunteers the sedative-hypnotic effects of diazepam and mitrazepam were studied. Three dose levels of each drug were used, so that dose-effect curves could be produced. The most reliable results were obtained with the CFF method, and significant dose-effect relations could be demonstrated. The CFF deviation after diazepam initially related well to the concentration in blood serum, but after 4--6 hours the CFF depression vanished rapidly, while the drug concentration remained high. After nitrazepam the signs of drowsiness occurred similarly, while the drug concentration in serum showed on an average a slower rise. The effects began to disappear before the nitrazepam concentration had reached a peak. A rapid tachyphylaxis at the receptor sites seems to be responsible for this incongruity. Nitrazepam exerted significantly stronger sedative effects than diazepam, particularly when the respective serum concentrations were taken into account. This confirms that nitrazepam should be a more efficient sleeping drug, although diazepam also has considerable sedative-hypnotic action.
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