Physiological disposition and metabolism of 3,4-dimethoxyphenylethylamine in the rat.

Abstract

DMPEA is taken up rapidly by rat tissues after i.p. administration of 75 mg DMPEA·HCl/Kg and at 5 min the following maximal concentrations (μg/g or ml) were found: kidney, 158; liver, 141; spleen, 110; heart, 41; plasma, 20; skeletal muscle, 15 and brain, 8. Approximately 90 % of this compound disappeared from these tissues within 60 min. Subcellular fractionation of brain and liver homogenates revealed that approximately 70% of the DMPEA found in these organs was present in the cytoplasmic fraction and little of the compound was found in the nuclear (16%), mitochondrial (7 %) or microsomal (7 %) fractions. Pretreatment with iproniazid increased brain and liver levels of DMPEA whereas cold stress and reserpine were without effect.In vitro studies showed that DMPEA is metabolized most rapidly in liver; progressively less metabolism was found in heart, brain, lung, kidney and spleen homogenates. Subcellular fractionation of liver and brain homogenates implicated the mitochondrial fraction as the major site of metabolism (approximately 75 %) and little activity was observed in the nuclear (18%), microsomal (5%) or cytoplasmic (2%) fractions. DMPEA did not affect concentrations of various amino acids in rat brain but increased levels of brain serotonin slightly. Quantities of DMPEA found in brain appeared to correlate directly with changes in the rope climbing performance of rats. The data presented suggest a direct mode of action of DMPEA in the central nervous system.