Evidence for presynaptic antagonism by amantadine of indirectly acting central stimulants

Abstract

In mice, amantadine pretreatment (150 mg/kg, but not 10 mg/kg, 2 h prior to testing) markedly inhibited the locomotor stimulation produced by submaximal doses of d-amphetamine, amfonelic acid, methylphenidate, caffeine, memantin, phencyclidine, and cocaine. A 50-mg/kg dose was ineffective in blocking the effects of caffeine and memantin, but blocked the responses to the other five stimulants. Amantadine did not modify the locomotor stimulant effect of apomorphine in reserpinized mice. These results indicate that amantadine acts as a presynaptic antagonist to the above seven stimulants. Even the highest dose of amantadine did not modify the hyperactivity induced in mice by morphine and levorphanol. This result is consistent with evidence showing opiate actions at postsynaptic striatal neurons, sites where presumably amantadine is unable to exert an antagonist effect. Amantadine did not modify the central depressant effects of ethyl alcohol and pentobarbital. Amantadine could be of value as a pharmacological tool in understanding the mode of action of central stimulants, and in the management of stimulant abuse. The present data do not support the currently held view that the antiparkinsonism effect of amantadine results from its ability to potentiate the central effects of dopamine.

Evidence for monoaminergic involvement in triadimefon-induced hyperactivity

“…Methylphenidate has aiso been previously shown to increase motor activity (Ward et al, !981;Brenneman et at. 1982;Menon et al 1984). In the present study hyperactivity following methylphenidate exposure was significant only when rats were tested for 2 h, but not for 1 h, This was most likely due to an interaction of the tack of effect on initial activity (i.e., no change in activity in the first 5 rain) and the level of hyperactivity sustained throughout she rest of the experiment.…”

Behavioral effects of aminoadamantane class NMDA receptor antagonists on schedule-induced alcohol and self-administration of water in mice

“…In addition to these pharmacodynamic differences, amantadine also exhibits actions on dopaminergic systems in the brain. For example, amantadine was shown in mice to inhibit the locomotor stimulation produced by submaximal doses of indirect dopamine agonists, such as d-amphetamine, amfonelic acid, methylphenidate, and cocaine (Menon et al 1984). This may be due, in part, to its ability to compete with the dopamine transporter (Mirovsky et al 1995;Page et al 2000;Peeters et al 2002) and enhance dopamine synthesis by induction of dopa-decarboxylase activity (Fisher et al 1998).…”

“…Testing of each drug commenced the day after saline treatment. Optimal drug doses were determined from the literature (Menon et al 1984;Piasecki et al 1998;Parsons et al 1999) along with pilot studies. After each SIP test, all mice were returned to their home cage and given enough food to maintain 85% of their baseline weight.…”

Effect of bromantane, a new immunostimulating agent with psychostimulating activity, on the release and metabolism of dopamine in the striatum of freely moving rats. A microdialysis study

“…Its mechanism of action has not been studied in sufficient detail. The dopaminergic and serotoninergic systems play an important role in the realization of the effects of adamantane derivatives [1,2,4,8,11,12,14]. In a concentration range of 50-500 ~M bromantane notably reduces serotonin reuptake by rat brain synaptosomes, inhibiting to a lesser exteat the reuptake of dopamine.…”