Conventional levodopa

The low levels of dopamine in the brains of patients with PD cannot be supplemented with peripherally administered dopamine itself, due to its inability to cross the blood-brain barrier; however, orally administered levodopa, a natural dopamine precursor, is able to cross the blood-brain barrier and pass into the brain where it is converted into dopamine (see Figure 14).

The exact location of levodopa's conversion to dopamine in the brain is unknown but, within the striatum, the enzyme responsible for conversion (aromatic-L-amino-acid decarboxylase [AADC]) is located principally in the nerve terminals of nigrostriatal dopaminergic neurons.^[23]

Levodopa therapy is highly effective in controlling most of the symptoms of PD, dramatically reducing the disability and mortality associated with the condition.

Once in the body, levodopa is metabolized by several different enzymes, with dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT) being the most significant. Conventional levodopa is always given with a DDC inhibitor (DDCI; carbidopa or benserazide) to reduce this peripheral breakdown of levodopa and enhance delivery of levodopa into the brain.

Levodopa is currently available in several formulations. However, because of the benefit of taking levodopa with a DDCI, levodopa tablets or capsules now always include either carbidopa or benserazide in the same formulation (Table 4).

Levodopa therapies

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More than 30 years after its discovery, levodopa remains the gold standard therapy for PD, and a large majority of patients who commence treatment with an alternative drug will eventually require the improved symptomatic control provided by levodopa therapy.

Parkinsons

Disease Management

Conventional levodopa