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Journal of Pharmacology And Experimental Therapeutics, Vol. 118, Issue 1, 84-89, 1956
Copyright © 1956 by American Society for Pharmacology and Experimental Therapeutics

PERSISTENCE OF RESERPINE ACTION AFTER THE DISAPPEARANCE OF DRUG FROM BRAIN: EFFECT ON SEROTONIN

Sidney M. Hess 1, Parkhurst A. Shore 2, and Bernard B. Brodie 2

1 Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education and Welfare, Bethesda, Md.
2 Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Public Health Service, U. S. Department of Health, Education and Welfare, Bethesda, Md.

Reserpine, administered intravenously as a single large dose to rabbits, readily entered the brain, reaching a maximal level within 15 minutes when it was considerably higher than that concurrently present in plasma. It rapidly disappeared from the brain, during the time the central actions were becoming more marked, and was almost undetectable in about 4 hours. The drug also disappeared rapidly from plasma and other tissues and was virtually absent from the body within 13 hours.

Reserpine produced profound central effects, including sedation, which persisted for about 48 hours. These effects were temporally related to a marked change in brain serotonin and not to the concentration of reserpine. These results are highly indicative that reserpine does not act per se but causes its central effects by producing a persistent change in brain serotonin.

Submitted on May 12, 1956




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Copyright © 1956 by the American Society for Pharmacology and Experimental Therapeutics.