Levodopa therapy from the neuroprotection viewpoint. From a clinical outlook.

There are many reports indicating the existence of free radical adducts in the Parkinson's disease (PD) brain. However, levodopa may have two aspects in its characteristics, one is that levodopa is a source of free radicals in the pathogenesis of PD, and the other is that it is the precursor of the most efficient transmitter in dopaminergic neurons from the viewpoint of therapy. Dopamine (DA) supplemented by levodopa acts as a neural transmitter and as a dopaminergic receptor-mediated trophic agent. From studies using rodent models of parkinsonism, physical exercise potentially induces neurotrophins in the brain and protects or enhances the regeneration of nigrostriatal neurons. In our preliminary experiment, the potential effects of physical exercise on motor and psychological symptoms were observed, suggesting that physical exercise may, to a certain extent, modulate pathological conditions in the brain. On the basis of the above we conclude that DA supplementation in PD potentially increases the levels of neurotrophins in a dopaminergic receptor-mediated manner, and secondarily enhances mobility (physical exercise). In general, levodopa demand increases with disease progression, and physical therapy is more important in advanced stages. To obtain good outcomes of physical exercise, it is essential to maintain a good medical control, particularly at the advanced stages of PD. From these results, it can be speculated that levodopa exerts some neuroprotective effects as long as the dose is not excessively high.