Metatyrosine as a tool for selective protection of catecholamine stores against reserpine

Abstract

Metatyrosine, injected i.p. to mice in single or repeated doses of 100 to 400 mg/kg, caused a marked, though short-lasting depletion of brain noradrenaline (NA) and dopamine (DA) and of heart NA, whereas brain 5-hydroxytryptamine (5-HT) was essentially unaffected. When given in repeated doses shortly before and after the injection of reserpine (3 mg/kg i.p.), metatyrosine caused partial but significant protection against the catecholamine-depleting action of reserpine in the brain, whereas brain 5-HT and heart NA were not, or at most slightly, protected. These effects on monoamine levels were observed 24 hr after the injection of reserpine. The protective activity of metatyrosine on brain NA was absent in animals pretreated with protriptyline (repeated doses of 10 mg/kg i.p.), whereas brain DA remained protected. Metatyrosine, with or without protriptyline pretreatment, markedly prevented the gross syndrome induced by reserpine. The hypothermic action of reserpine was only partially prevented. It is concluded that depletion of brain catecholamines, notably DA, plays an important role in the gross behavioural action of reserpine.