Studies on the Mechanism of Action of Amantadine

Abstract

I The effect of amantadine hydrochloride on various aspects of catecholamine metabolism in the rat brain has been investigated. 2 Amantadine failed to have any significant effect on brain concentrations of dopamine or noradrenaline even when administered daily for 9 days. 3 Amantadine had no effect on the rate of decline of noradrenaline and dopamine concentrations after a-methyl-p-tyrosine.4 In vitro, amantadine inhibited dopamine uptake into synaptosomes only at high concentrations, and caused little release of dopamine from synaptosomes. SThere is no evidence from these results to suggest that the anti-Parkinsonian effect of amantadine is related to an action on dopaminergic mechanisms.

Persistent cognitive dysfunction after traumatic brain injury: A dopamine hypothesis

“…Doses of AMH given to patients are also somewhat variable due to a lack of correlation between plasma concentrations and therapeutic effects (Aoki and Sitar, 1988). In vitro studies have shown that doses required to affect DA uptake are higher than those used clinically with no significant difference in DA kinetics until concentrations of 40–80 mg/kg were given (Baldessarini et al, 1972; Brown and Redfern, 1976; Page et al, 2000). In brain injury patients the optimal dose of AMH has ranged from 50 to 400 mg/day given orally (Gualtieri et al, 1989).…”

Locomotor effects of amantadine in the mouse are not those of a typical glutamate antagonist

“…There are various reports that amantadine can increase the synthesis and/or release of dopamine, or block its reuptake (Brown and Redfern, 1976;Heikkila and Cohen, 1972;Scatton et al, 1970;Von Voigtlander and Morre, 1971), but it is doubtful if the high extraneuronal concentrations of amantadine required to effect the release of dopamine experimentally could be attained during routine antiparkinson therapy in man (Pacifici et al, 1976). Moreover, a presynaptic modulatory action is made less likely by the fact that amantadine can promote motor activity in animals even after dopamine synthesis and release have been abolished (Maj et al, 1972;Papeschi, 1974), and so its precise mode of action has remained enigmatic.…”

Nasogastric Medication for Perioperative Parkinson's Rigidity during Anaesthesia Emergence

“…Amantadine is a second-line agent which is believed to increase the bioavailability of dopamine within the central nervous system. However, consensus on the precise mechanism of action is lacking 1,3 . It has a half-life of 16 hours and onset of action of 60 to 90 minutes 1 .…”

“…It is known that these patients are at greater risk of perioperative complications 1,3,4 involving neurological, respiratory, cardiovascular, gastrointestinal and autonomic systems. What is less clear is how to optimally manage these patients under anaesthesia.…”