Levodopa - an exotoxin or a therapeutic drug?

Auto-oxidation of levodopa generates toxic metabolites, such as free radica ls, semiquinones and quinones. In vitro, levodopa is a powerful toxin that is lethal to cultures of neurones. This raises the concern that levodopa ma y also be toxic in vivo, and that chronic treatment with levodopa could ind uce further damage to nigrostriatal neurones in patients with Parkinson's d isease, accelerating the natural predetermined rate of disease progression. Although a few animal studies have shown that chronic levodopa may be toxi c in vivo, most others report that it is not. The few available clinical st udies also indicate that the course of Parkinson's disease is not accelerat ed by chronic systemic treatment with levodopa.