BINDING AND RELEASE OF METARAMINOL: MECHANISM OF NOREPINEPHRINE DEPLETION BY ALPHA-METHYL-M-TYROSINE AND RELATED AGENTS.

l -Metaraminol, but not d-metaraminol or α-methyl- m -tyramine, is rapidly taken up and retained by heart. After treatment with l -metaraminol or dl -α-methyl- m -tyrosine (α-MMT), metaraminol persists for days in heart and brain, but disappears rapidly from liver. Metaraminol is not taken up by hearts of immunosympathectomized rats. Uptake is inhibited by drugs known to inhibit norepinephrine uptake (reserpine, imipramine, guanethidine). Metaraminol in heart is released by norepinephrine or by drugs known to release norepinephrine (reserpine, guanethidine, tyramine). A stoichiometric relationship is found at most times between norepinephrine depletion and metaraminol uptake. d -Metaraminol is not retained by heart, nor does it deplete heart norepinephrine. It is concluded that l-metaraminol is the active norepinephrine-depleting agent following injection of α-MMT and that metaraminol exchanges with norepinephrine at adrenergic nerve endings on a mole-for-mole basis.