The combined use of α-methyltyrosine and threo-dihydroxyphenylserine—selective reduction of dopamine levels in the central nervous system

Abstract

Dihydroxyphenylserine- α- 14C (DOPS- α- 14) is taken up into mouse brain and decarboxylated to form norepinephrine- 14C. The combined use of nontracer doses of this amino acid ( threo- or erythro-DOPS) and the tyrosine hydroxylase inhibitor, α-methyltyrosine ethyl ester, causes a 50 per cent depletion of dopamine in the central nervous system in mice while leaving norepinephrine levels unchanged. Without threo-DOPS, α-methyltyrosine depletes both norepinephrine and dopamine levels to less than one-half their normal values. dl- Threo-DOPS rapidly replenishes norepinephrine levels in reserpine-treated mice, but does not cause the awakening effect shown by l-DOPA under the same conditions. It is suggested that the reversal of the reserpine syndrome by l-DOPA is due to formation of dopamine rather than norepinephrine in the central nervous system.