Abstract
The products of norepinephrine-H3 metabolism in the rat are excreted in two phases. The metabolites excreted during the first phase indicate that O-methylation is the major route of metabolism of unbound norepinephrine. After several hours, during the second phase of radioactivity excretion, the pattern of metabolites is changed. The norepinephrine-H3 which had been bound and slowly released seems to be metabolized primarily by monoamine oxidase.
Drugs which cause tissue depletion of norepinephrine may do so by permitting intracellular destruction before activation, or by extracellular release of the catecholamine into an active form, or both of these. Tyramine, DMPP, and acetylcholine cause release of active norepinephrine into the circulation. Reserpine, guanethidine, and α-methyldopa deplete tissues predominantly by allowing intracellular destruction of the catecholamine by monoamine oxidase. When MAO is inhibited, reserpine, like tyramine, results in release of active norepinephrine. These biochemical findings are discussed in relation to the pharmacological effects of these drugs.
Footnotes
- Received January 11, 1963.
- Accepted February 15, 1963.
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