The role of brain monoamines in the anti-Parkinsonian action of amantadine.

  • F. Brown

Student thesis: Doctoral ThesisPhD


The pharmacology of amantadine (1-aminoadamantane, 1-amino-tricyclo-[,7]-decane) hydrochloride (I) is reviewed with respect to its anti-Parkinsonian action. The following results were obtained in this pharmacological study of I. 1. Two groups of 10 rats treated chronically with I in the drinking water both consumed less food and water and gained less body weight than similar control groups. 2. Dopamine (DA) and noradrenaline concentrations in rat brain and their turnover, measured by inhibition of synthesis, were not significantly changed by acute or chronic treatment with I. 5-Hydroxytryptamine concentration was not significantly affected by acute treatment with I. 3. The concentrations of the DA metabolites, 3, 4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic acid, in rat and mouse brain were not significantly changed by acute treatment with I. 4. No significant effects of I on the subcellular distribution or stability of DA in rat brain homogenates were observed. 5. I non-competitively inhibited dopamine uptake (Ki = 1.25 x 10-4) by synaptosome preparations of rat corpus striatum. Substantial dopamine release was not obtained in these preparations but a weak effect would not have been distinguished from the relatively weak effect on uptake. I had no particular specificity for inhibiting dopamine uptake as compared to other brain amines. 6. I given intraperitoneally or intracerebroventricularly caused a dose dependent fall in temperature of rats housed at 4°C or mice at 21°C. The hypothermic effect of I was not reduced by dopamine receptor blocking agents. I did not reverse reserpine-induced hypothermia. The mode of action of I in Parkinson's disease is discussed. Dopamine release from hyperactive surviving dopaminergic neurones in the Parkinsonian striatum is proposed as the principal mode of action of I.
Date of Award1975
Original languageEnglish
Awarding Institution
  • University of Bath

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