Levodopa - Is toxicity a myth?

Whether a drug such as levodopa, which is prescribed for long periods, may be toxic is a legitimate and even indispensable question. The problem is no different from that posed by other drugs-such as calcium antagonists, anti hypertensives, or hormones-normally prescribed for chronic diseases. What, however, is meant in this context by "toxic" (from the Greek toxicon, meani ng poison)? Irrevocable damage such as cell loss should not be confused wit h reversible side effects resulting from cell dysfunction. Clinically or ex perimentally, levodopa has not been shown to accelerate neurodegeneration o r cause permanent impairment of cell function in a manner that would result in irreversible side effects. These data have been reasonably well establi shed in vivo in animals and humans, although preliminary studies suggesting that levodopa is a trophic factor remain unconfirmed. Like oxygen or calci um, levodopa can be toxic in vitro when it is present in high concentration s or in the absence of glial cells. However, glial cells are much more nume rous than neurons in vivo, so these conditions cannot simply be extrapolate d to three-dimensional brain structures in which protective interactions wi th the cellular environment abound. Because levodopa remains the most effec tive treatment available for Parkinson's disease, questions regarding timin g or manner of administration of the drug should arise not because levodopa is toxic to nerve cells, but because it causes reversible side effects. Wh en the elementary rules of substitutive therapy to provide maximum comfort while limiting side effects are followed, we need not fear that levodopa is dangerous unless the contrary is proven.