On the mechanism of the norepinephrine release produced by a-methyl-meta-tyrosine

strated that a-methyl-3,4-dihydroxyphenylala-nine (a-methyl-dopa), a-methyl-meta-tyrosine (a-MMT), and their corresponding amines are potent releasing agents of norepinephrine. Subse-quent studies from other laboratories (Sourkes et al., 1961; Gessa et al., 1962) have confirmed and extended these observations. Following ad-ministration of a single dose of a-MMT or its decarboxylated product, a-methyl-meta-tyramine (a-MMtyramine), norepinephrine in brain and heart falls to very low levels, the depletion per-sisting for many days. In a preliminary communi-cation Udenfriend et al. (1961) discussed the mechanism of the release and presented some evi-dence which showed that the long-lasting deple-tion was not due to a mole-for-mole displacement of the norepinephrine by a-MMT. Since a-MMT is an excellent substrate of dopamine $-oxidase, yielding aramine (Creveling et al., 1962a), and since the latter has been demonstrated in tissues of animals receiving a-MMT (Carlsson and Lindqvist, 1962), studies on mechanism must take into account the conversions shown in figure 1. In the present report it is shown that both a-MMtyramine and aramine are potent norepi-nephrine releasing agents. Aramine is, on a dose basis, about as active as reserpine. This is in agree-ment with Carlsson and Lindqvist (1962) and Gessa et al. (1962). The potency of these amines suggests that they are responsible for the nor-epinephrine releasing action of the amino acid, a-MMT. Experiments with decarboxylase in-hibitors confirm this suggestion. It has also been shown that far less than stoichiometric amounts of a-MMtyramine or aramine (either adminis-tered as such or formed from a-MMT) are re-quired to bring about release and maintain deple-tion of norepinephrine. With maximal amine levels of 0.1 to 0.3 millimicromole per grain of heart, 7 to 8 millimicromoles of norepinephrine may be released. Twenty-four hours later even these traces of amines are gone but the norepi-nephrine depletion remains