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Journal of Pharmacology And Experimental Therapeutics, Vol. 183, Issue 2, 307-315, 1972
Copyright © 1972 by American Society for Pharmacology and Experimental Therapeutics

IPRINDOLE-AMPHETAMINE INTERACTIONS IN THE RAT: THE ROLE OF AROMATIC HYDROXYLATION OF AMPHETAMINE IN ITS MODE OF ACTION

J. J. FREEMAN 1 and F. SULSER 1

1 Department of Pharmacology, Vanderbilt University School of Medicine, and Tennessee Neuropsychiatric Institute, Nashville, Tennessee

The present investigations were undertaken to study the mechanism by which iprindole enhances the psychomotor stimulation (locomotor and stereotyped activity) of amphetamine and to elucidate the role of the hydroxylated metabolites of amphetamine in its mode of action. The enhanced psychomotor stimulation and the increased levels of amphetamine in tissue after iprindole pretreatment resulted from an inhibition of the p-hydroxylation of amphetamine. Iprindole markedly reduced the accumulation of p- hydroxyamphetamine in urine and p-hydroxynorephedrine in tissue after the administration of amphetamine. Since pretreatment with iprindole enhanced the central action of amphetamine and did not prevent the initial depletion of norepinephrine in brain or heart, the formation of the hydroxylated metabolites of amphetamine does not seem to be required for these pharmacological or biochemical effects. The maintenance of depletion of norepinephrine caused by amphetamine, however, was associated with the accumulation of p-hydroxynorephedrine in tissue. Unlike desipramine, iprindole altered neither the initial accumulation nor the metabolism of tritiated norepinephrine in brain or heart. The results show that iprindole is a "cleaner" tool to study the mechanism of action of amphetamine and suggest that a blockade of the neuronal membrane pump is not a requirement for the therapeutic efficacy of tricyclic antidepressants.

Submitted on February 16, 1972
Accepted on June 30, 1972




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R. Fuller and S Hemrick-Luecke
Long-lasting depletion of striatal dopamine by a single injection of amphetamine in iprindole-treated rats
Science, July 11, 1980; 209(4453): 305 - 307.
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Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics.