The two faces of L-DOPA: benefits and adverse side effects in the treatment of Encephalitis lethargica, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis

Med Hypotheses. 2004;62(2):177-81. doi: 10.1016/S0306-9877(03)00318-9.

Abstract

Parkinson's disease, encephalitis lethargica, multiple sclerosis and amyotrophic lateral sclerosis patients all display two distinct types of symptoms. Some of these are due directly to a deficiency of dopamine and are quickly reduced by laevodihydroxyphenylalanine (L-DOPA). The second set, however, are the result of neurological damage caused by metabolites of dopamine, which include dopachrome and other chrome indoles that are both hallucinogenic and neurotoxic. If this hypothesis is correct, three corollaries follow. Patients of all four disorders should display excessive oxidative stress, natural methyl acceptors should delay development and elevated antioxidant supplementation, given with L-DOPA, ought to prolong the "honeymoon" period in which the benefits of the drug out weigh its subsequent disadvantages. A literature review suggests that all three corollaries are probably correct.

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Antioxidants / therapeutic use*
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / therapeutic use
  • Dopamine Agents / adverse effects
  • Dopamine Agents / therapeutic use
  • Dyskinesia, Drug-Induced / etiology
  • Gastrointestinal Diseases / chemically induced
  • Hallucinations / chemically induced
  • Humans
  • Levodopa / adverse effects*
  • Levodopa / therapeutic use*
  • Multiple Sclerosis / drug therapy*
  • Oxidative Stress / drug effects
  • Parkinson Disease / drug therapy*
  • Parkinson Disease, Postencephalitic / drug therapy
  • Psychoses, Substance-Induced / etiology
  • Sleep Initiation and Maintenance Disorders / chemically induced
  • Vitamin B Complex / therapeutic use*

Substances

  • Antioxidants
  • Antiparkinson Agents
  • Dopamine Agents
  • Vitamin B Complex
  • Levodopa