Abstract
Summary
Intravenous administration of high doses of aspirin, phenylbutazone or naproxen to rats which had just regained the righting reflex from an anesthetic dose of thiopental caused them to again lose their righting reflex. Naproxen was also shown to reinduce thiopental sleep in rabbits and the reinduction of sleep was correlated with a marked elevation in the concentration of unbound thiopental in plasma. Furthermore, high concentrations of aspirin, phenylbutazone, indomethacin, mefenamic acid and naproxen were shown to displace thiopental from rabbit plasma proteins in vitro. These results suggest that high concentrations of nonsteroidal anti-inflammatory agents, all of which strongly bind to plasma proteins, effectively displace thiopental from plasma proteins, thus leading to reinduction of its action.
Thanks are expressed to Mrs. S. Barrows, Mrs. F. Schein, Miss K. Kamachi and Mr. B. Rice for excellent technical assistance.
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