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Journal of Pharmacology And Experimental Therapeutics, Vol. 127, Issue 2, 103-109, 1959
Copyright © 1959 by American Society for Pharmacology and Experimental Therapeutics

BIOCHEMICAL AND PHARMACOLOGICAL STUDIES OF RO 1-9569 (TETRABENAZINE), A NON-INDOLE TRANQUILIZING AGENT WITH RESERPINE-LIKE EFFECTS

Gertrude P. Quinn 1, Parkhurst A. Shore 1, and Bernard B. Brodie 1

1 Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

A method is described for the estimation of Ro 1-9569 (tetrabenazine), a non-indole synthetic derivative of benzoquinolizine, in biological tissues.

After intravenous injection in the rabbit, Ro 1-9569 is rapidly and almost completely metabolized. The duration of action of the drug is limited to the time that appreciable amounts of the compound remain in the body.

The drug has a selective action on brain serotonin anti norepinephrine, releasing little or none of these amines peripherally. Consequently, the drug does not elicit diarrhea, which occurs with the release of serotonin in the intestines, or hypotemision associated with the depletion of norepinephrine from sympathetic nerve endings.

Ro 1-9569 has a greater effect on brain norepinephrine than on brain serotonin. However, the sedative effect of the drug seems to be related to the change in brain serotonin rather than norepinephrine.

Animals given Ho 1-9569 immediately before reserpine respond as though they received only Ro 1-9569. It is concluded that Ro 1-9569 and reserpine compete for the same receptor sites.

Submitted on April 27, 1959




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