TISSUE CONCENTRATIONS OF P-HYDROXYNOREPHEDRINE IN RATS INJECTED WITH D-AMPHETAMINE - EFFECT OF PRETREATMENT WITH DESIPRAMINE

This report shows that p-hydroxynorephedrine accumulates in brain and heart of rats given d-amphetamine. The tissue content of p-hydroxynorephedrine declines slowly while that of the parent compound has a halflife of about 1 hour. The presence of this metabolite in tissues may be of value to explain the persistent depletion of NE stores induced by d-amphetamine. A pretreatment with desipramine blocks the accumulation of p-hydroxynorephedrine and prevents the depletion of cardiac NE elicited by the parent compound. Although the metabolite fails to accumulate when rats are pretreated with desipramine and then given d-amphetamine, the hyperthermia lasts longer than in rats given only d-amphetamine. Neither depletion of peripheral NE nor the accumulation of p-hydroxynorephedrine are absolute requirements for hyperthermia, piloerection and increased motor activity caused by d-amphetamine. © 1969.