Amantadine (Symmetrel) is an antiviral agent whose dopaminergic properties make it effective in the treatment of Parkinson’s disease and for prophylaxis against the parkinsonian side effects of neuroleptic agents. Although amantadine is no longer recommended for the treatment or prophylaxis of influenza because of resistance, it has been studied as a potential treatment for hepatitis C, Huntington’s disease, brain injury or encephalopathy, and cocaine dependence. Its effects in acute overdose have been associated with seizures, arrhythmias, and death. Withdrawal from amantadine has also been linked to neuroleptic malignant syndrome.

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   Mechanism of toxicity

   
   
   
   
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      Amantadine is thought to increase dopamine levels in the peripheral and central nervous systems by enhancing the release of dopamine and preventing dopamine reuptake. It also acts as a noncompetitive antagonist at the N-methyl-d-aspartate (NMDA) receptor. It blocks potassium and sodium channels in cardiac myocytes, leading to QT prolongation and widened QRS intervals. In addition, it has anticholinergic properties, especially in overdose.

      
      
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      Pharmacokinetics. Peak absorption 1–4 hours; volume of distribution (Vd) 4–8 L/kg. Eliminated renally with a half-life of 7–37 hours (see also Table II–61).

   
   
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