TY - JOUR T1 - REGIONAL STUDIES OF CATECHOLAMINES IN THE RAT BRAIN. IV. EFFECTS OF DRUGS ON THE DISPOSITION AND METABOLISM OF H<sup>3</sup>-NOREPINEPHRINE AND H<sup>3</sup>-DOPAMINE JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 30 LP - 41 VL - 153 IS - 1 AU - Jacques Glowinski AU - Julius Axelrod AU - Leslie L. Iversen Y1 - 1966/07/01 UR - http://jpet.aspetjournals.org/content/153/1/30.abstract N2 - The effects of reserpine, a monoamine oxidase inhibitor, Catron (pheniprazine), amphetamine and desmethylimipramine (DMI) on the metabolism of dl-H3-norepinephrine were examined in cerebellum, medulla oblongata, hypothalamus, striatum, midbrain, hippocampus and cortex of the rat brain. Reserpine reduced the accumulation of H8-norepinephrine to varying extents in the different brain regions. In reserpine-pretreated animals, there was also an elevation in the levels of H3-deaminated metabolites and a fall in H3-normetanephrine in all regions. After Catron, there was an increased accumulation of H3-norepinephrine in all areas of the brain except in the striatum; deaminated metabolites were severely reduced, while H3-normetanephrine levels were strikingly elevated in all areas of the brain, including the striatum. Both amphetamine and DMI reduced the accumulation of H3- norepinephrine in the cerebellum, medulla oblongata and hypothalamus, but produced only small changes in other areas. Amphetamine caused a striking elevation in the levels of H3-normetanephrine throughout the brain, while DMI produced only small elevations in the medulla oblongata and cortex. O-methylated deaminated metabolites were unaffected by either drug, though catechol deaminated metabolites were reduced, particularly after amphetamine. H3-amphetamine was evenly distributed in the brain at a concentration of about 8 µg/g (5 x 10-3M) after an intraperitoneal injection of 15 mg/kg. Amphetamine at this concentration almost completely inhibited the enzymatic deamination of H3-norepinephrine in vitro. The levels of H3-norepinephrine were reduced in the medulla oblongata, cerebellum and hypothalamus after the intraventricular injection of H3-dopamine in d- amphetamine- or DMI-pretreated animals. H3-dopamine levels in these regions and in the striatum were unaffected or increased after amphetamine or DMI. The Williams &amp; Wilkins Comapny ER -