Some actions of amantadine on peripheral tissues

Abstract

Amantadine has been tested on several peripheral preparations. It depressed responses of the chick isolated oesophagus to nicotine and preganglionic parasympathetic nerve stimulation without depressing responses to acetylcholine. It did not affect the amplitude or duration of action potentials in toad sciatic nerve. It enhanced the effects of noradrenaline and dopamine while reducing the effect of tyramine on the coaxially stimulated guinea‐pig ileum, isolated central artery of the rabbit ear and spontaneously beating guinea‐pig isolated atria preparations. Amantadine enhanced the depressor effect of dopamine in the rabbit.

Studies on the Mechanism of Action of Amantadine

“…This finding is supported by results of other workers (Baldessarini et al, 1972;Heikkila & Cohen, 1972;Herblin, 1972) although Heimans et al (1972) reported that amantadine would cause 50% inhibition of dopamine uptake into striatal homogenates at a concentration as low as 3.6 JiM.…”

“…A dopamine releasing property for amantadine has been claimed by many workers (Stromberg, Svensson & Waldeck, 1970;Stromberg & Svensson, 1971;Farnebo et al, 1971) while others have found it to be a less effective releasing agent than uptake blocking agent (Heikkila & Cohen, 1972;Heimans et al, 1972). As has already been mentioned, it is difficult in an in vitro system such as we have used to distinguish between uptake blockade and amine release.…”

“…However, there is a lack of concensus as to the exact mechanism of action of the drug. Direct stimulation of dopamine receptors (Papeschi, 1974), blockade of neuronal uptake (Fletcher & Redfern, 1970;Heimans, Rand & Fennessy, 1972;Baldessarini, Lipinski & Chace, 1972), catecholamine release (Scatton, Cheramy, Besson & Glowinski, 1970;Von Voigtlander & Moore, 1971;Stromberg & Svensson, 1971;Farnebo, Fuxe, Goldstein, Hamberger & Ungerstedt, 1971) and increased synthesis (Scatton et al, 1970) have all been suggested to be responsible. We have investigated this problem by examining the effect of amantadine on brain concentrations of catecholamines, on the turnover of these amines in the brain, and on the uptake and release of dopamine from isolated synaptosome preparations.…”

The Effect of Anti-Parkinsonian Drugs on Chlorpromazine-Induced Depression of Operant Behaviour

“…Later ¿-dopa and amantadine were introduced into the treatment of Parkinson's disease (22) and the anti-parkinsonian effect of apomorphine is known as well (for review see 16). Both apomorphine (1,8) and amantadine (9)(10)(11)26) facilitate dopamin ergic mechanisms and, having no anticholinergic effect (20), they must be differ entiated from the central anticholinergics.…”