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Amantadin e tremor, a 5-hydroxytryptamine-mediated response?

B Cox, S J Tha

    European Journal of Pharmacology
    |February 1, 1975
    PubMed
    Summary
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    Amantadine-induced tremor in mice is linked to central nervous system (CNS) transmitters. Findings suggest amantadine affects serotonin (5-HT) receptor sensitivity, potentially explaining tremor and its anti-Parkinson effects.

    Area of Science:

    • Neuropharmacology
    • Central Nervous System (CNS) Research

    Background:

    • Amantadine is used to treat Parkinson's disease.
    • The neurochemical mechanisms underlying amantadine's side effects, like tremor, are not fully understood.

    Purpose of the Study:

    • To investigate the neurochemical basis of amantadine-induced tremor.
    • To explore the role of central nervous system (CNS) transmitters in amantadine's tremorgenic action.

    Main Methods:

    • Administered amantadine and other drugs (mebanazine, reserpine, diethyldithiocarbamate, p-chlorophenylalanine) to mice and rats.
    • Measured changes in brain catecholamine and 5-hydroxytryptamine (5-HT) levels.
    • Assessed amantadine's effect on 5-hydroxy-indoleacetic acid (5-HIAA) concentrations.
    • Examined amantadine's influence on rat fundus 5-HT receptor sensitivity.

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    Main Results:

    • Amantadine-induced tremor is modulated by noradrenaline, dopamine, and 5-HT balance.
    • Drugs depleting catecholamines exacerbated amantadine tremor; p-chlorophenylalanine (depleting 5-HT) antagonized it.
    • Amantadine decreased rat brain 5-HIAA levels, particularly when 5-HT was elevated.
    • Amantadine increased 5-HT receptor sensitivity in rat fundus.

    Conclusions:

    • Amantadine's tremorgenic effects may stem from altered CNS transmitter balance, specifically involving 5-HT receptor sensitivity.
    • This mechanism could also relate to amantadine's therapeutic anti-Parkinsonian activity.