TETRAHYDROPAPAVEROLINE: AN ALKALOID METABOLITE OF DOPAMINE IN VITRO

¹ Metabolic Research Laboratory, Veterans Administration Hospital and Department of Biochemistry, Baylor College of Medicine, Houston, Texas

Tetrahydropapaveroline (THP) has been found to be a quantitatively important metabolic product of dopamine-C¹⁴ in rat brainstem and liver homogenates. Methods have been developed for the separation and isolation of THP from tissue extracts. The identity of THP as a metabolite of dopamine in tissue homogenates has been confirmed by thin layer and gas-liquid chromatography and by infrared spectrophotometry. The relative formation of THP in vitro was greatly dependent upon the substrate concentration and upon the amount of nicotinamide adenine dinucleotide available for further oxidation of 3,4-dihydroxyphenylacetaldehyde to 3,4-dihydroxyphenylacetic acid. THP was the major metabolite of dopamine in the absence of exogenous coenzymes with both liver or brainstem homogenates. Incorporation of nicotinamide adenine dinucleotide or reduced nicotinamide adenine dinucleotide into incubation mixtures of liver homogenates essentially abolished THP production and markedly enhanced the formation of the acid or neutral metabolites. However, THP remained the major catabolite of the intermediate aldehyde in brain under all conditions. Consequently, the relative amount of dopamine diverted to THP assumed appreciable importance under conditions limiting the oxidation or reduction of 3,4-dihydroxyphenylacetaldehyde. Since THP is known to be pharmacologically active, formation of this alkaloid may be of functional importance.