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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Circadian phase dependency of the effects of different beta-receptor blocking drugs on motor activity of rats. Importance of drug lipophilicity.

The effects of seven beta-receptor blocking drugs differing in lipophilicity by 3.5 orders of magnitude (propranolol, bupranolol, oxprenolol, metoprolol, sotalol, practolol, atenolol) were studied on the circadian rhythm in motor activity of light-dark-synchronized (light (L): 7-19 h, dark (D): 19-7 h) male rats. Motor activity after i.p. injection of saline or of the racemic mixtures of all drugs and the isomers of propranolol, bupranolol and practolol was measured in groups of 5 rats with a motimeter. Two doses of either drug were injected either at 7:30 a.m. in L or at 7:30 p.m. in D. In L the drugs did either not affect motor activity or even increased motility in comparison to saline. No dosage-dependency was observed in the drug effects in L. In contrast, during D a dosage-dependent decrease in motor activity was found for all compounds. ED50-values of decrease in motility during D were negatively correlated with lipophilicity (partition coefficient) of the compounds. No significant difference was found in the ED50-values of the isomers studied. The results clearly demonstrate a circadian phase dependency in the effects of beta-receptor blocking drugs on motor activity of rats. A dosage-dependent central depressant effect of the drugs could be observed only in D. It is concluded that the central depressant effects of beta-receptor blocking drugs are mainly due to the non-specific, lipophilic property of the drugs and not brought about by a specific blockade of central beta-adrenoceptors.[1]


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