Dopamine and noradrenaline releasing action of amantadine in the central and peripheral nervous system: A possible mode of action in Parkinson's disease

Abstract

Histochemical, biochemical and functional analyses of the effects of amantadine on the monoamine neurons in the peripheral and central nervous system of rat after various pretreatments have shown that amantadine, both in vivo and in vitro, is capable of releasing DA and NA from extragranular stores in central DA and NA neurons and in peripheral NA neurons. The functional findings on rotational behaviour, reflex activity and locomotor behaviour show that the increased release of DA and NA induced by amantadine in the brain also results in increased DA and NA receptor activity. Thus, both from a chemical and functional viewpoint amantadine has an amphetamine-like action. The potency of amantadine, however, is weak compared to that of amphetamine. A direct action on DA receptors can be excluded, since presynaptic stores of CA are required for amantadine to increase CA receptor activity.