Levodopa

Levodopa, also known as L-DOPA, is a dopaminergic medication which is used in the treatment of Parkinson's disease (PD) and certain other conditions like dopamine-responsive dystonia and restless legs syndrome.^[3][4] The drug is usually used and formulated in combination with a peripherally selective aromatic L-amino acid decarboxylase (AAAD) inhibitor like carbidopa or benserazide.^[3] Levodopa is taken by mouth, by inhalation, through an intestinal tube, or by administration into fat (as foslevodopa).^[3]

Side effects of levodopa include nausea, the wearing-off phenomenon, dopamine dysregulation syndrome, and levodopa-induced dyskinesia, among others.^[3] The drug is a centrally permeable monoamine precursor and prodrug of dopamine and hence acts as a dopamine receptor agonist.^[3] Chemically, levodopa is an amino acid, a phenethylamine, and a catecholamine.^[3] The major reason for enhanced risks for levodopa induced dyskinesia (LID) and OFF phases during late PD is the progressive dying of nigrostriatal dopaminergic neurons. This results in the conversion of levodopa into dopamine in serotonergic neurons (which cannot re-uptake dopamine and have no proper regulatory capacity for dopamine synthesis) becoming the major dopamine source in the dorsal striatum, leading to the striatal dopamine concentration following the pulsatile oral administration of levodopa with large fluctuations (see the schematic graph figure).^[4] On the other hand, in a disease like Segawa disease, in which dopamine synthesis is low but without progressive degeneration of dopaminergic neurons, lifelong administration of low doses of levodopa is believed to be without serious side effects.^[4]

Levodopa was first synthesized and isolated in the early 1910s.^[3] The antiparkinsonian effects of levodopa were discovered in the 1950s and 1960s.^[3] Following this, it was introduced for the treatment of Parkinson's disease in 1970.^[3]