EFFECT OF DRUGS ON THE UPTAKE AND METABOLISM OF H3-NOREPINEPHRINE

Abstract

Tyramine, amphetamine, cocaine, chlorpromazine, imipramine, reserpine, guanethidine and Dibenzyline (phenoxybenzamine) markedly reduced the concentration of administered H 3 - norepinephrine in the heart, spleen and (except for guanethidine) adrenal gland. These drugs lowered the H 3 -catecholamine concentration to a moderate degree in the liver. Imipramine was the only drug that lowered the H 3 -catecholamine in the skeletal muscle. The level of H 3 - normetanephrine was decreased by all these drugs in heart and spleen and in some cases in the adrenal gland and liver. Tyramine, amphetamine, cocaine, chlorpromazine, imipramine, reserpine, guanethidine and Dibenzyline also elevated the plasma levels of administered H 3 -norepinephrine for the first 5 minutes. The plasma levels of H 3 -normetanephrine were also raised to varying degrees. These drugs appear to be acting by preventing the entry and/or the binding of H 3 -norepinephrine. The following drugs had no significant effect on the tissue and plasma concentration of H 3 - norepinephrine and H 3 -normetanephrine: Regitine (phentolamine), dichlorisoproterenol, TM 10 B, hexamethonium and ouabain. The catechol-O-methyl transferase inhibitor, pyrogallol, elevated the concentration of H 3 - norepinephrine in heart, spleen, liver and muscle but not the adrenal gland and plasma, and lowered the concentration of H 3 -normetanephrine in these tissues except the heart and spleen. Catron, a monoamine oxidase inhibitor, had no effect on the tissue levels of H 3 -norepinephrine in these tissues (except skeletal muscle) and elevated the concentration of H 3 - normetanephrine in all tissues.