Using HPLC-ECD for the Comparison between Effects of Tranylcypromine and LY134046 on the Brain Adrenaline and Noradrenaline

Alexandar Marsden, Charles; W. Bennett, Giffery; Hatim Rashid, Imad

	Using HPLC-ECD for the Comparison between Effects of Tranylcypromine and LY134046 on the Brain Adrenaline and Noradrenaline
Iraqi Journal of Biotechnology
Article 1, Volume 12, Issue 2, 2013, Pages 34-47
Authors
Charles Alexandar Marsden; Giffery W. Bennett; Imad Hatim Rashid
Abstract
ABSTRACT:The effects and turnover of central adrenaline (Ad) has not been studied comprehensively as of noradrenaline (NA) and other amines. Effects both of the monoamine oxidase (MAO)- and phenylethanolamine N- methyl transferase (PNMT)- inhibitors were evaluated on the levels of Ad of certain brain regions, and compared with that of NA. The levels of the amines and metabolite in brain tissue extracts of male Wister rats i.p. administered either LY134046 or tranylcypromine were measured by high performance liquid chromatography- electrochemical detector (HPLC-ECD) and their changes from the controls were examined using the Student's unpaired t-test. The detection of Ad was at 2 nanoamper (nA) sensitivity, while of NA 3,4-dihydroxyphenyl acetic acid (DOPAC) and dopamine was at 10nA (LY134046) or 20nA (tranylcypromine). LY134046 causes significant decrease in the Ad levels of hypothalamus (-47%) and of brainstem (-73%) but was not detected in hippocampus or striatum both of the LY134046 and the controls. In contrast LY134046 causes significant increase in the dopamine and DOPAC of all tested brain regions, and in the NA of hypothalamus only (+70%). Tranylcypromine significantly increases the levels of NA and dopamine in all tested brain regions, whereas the Ad levels only increased in hypothalamus (+58%) and brainstem (+67%) but it was below the detection level in hippocampus or striatum. Though, DOPAC decreased in all the regions. The results indicates much higher tissue levels of the NA and DOPAC substances compared with the Ad and confirm the suggestion that the pharmacology of central Ad is analogous to that of central NA, with the exception of its synthesis. The significant decrease in the DOPAC of all brain regions though is more difficult to explain it could indicate that the LY134046 might also act on dopamine uptake sites which needs to be investigated.
Keywords
tranylcypromine; Dopamine; hypothalamus; brainstem

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