Levodopa is a metabolic precursor of dopamine. Also, It restores dopaminergic neurotransmission in the neostriatum by enhancing the synthesis of dopamine in the surviving neurons of the substantia nigra. In early disease, the number of residual dopaminergic neurons in the substantia nigra (typically about 20% of
normal) is adequate for conversion of levodopa to dopamine. Thus, in new patients, the therapeutic response to levodopa is consistent, and the patient rarely complains that the drug effects “wear off.”
Unfortunately, with time, the number of neurons decreases, and fewer cells can convert exogenously administered levodopa. Consequently, motor control fluctuation develops.
- Mechanism of action:
a. Levodopa: Dopamine does not cross the blood–brain barrier,
but its immediate precursor, levodopa, is actively transported into the CNS and converted to dopamine. Therefore, Levodopa must be administered with carbidopa. Without carbidopa, much of the drug is decarboxylated to dopamine in the periphery, resulting in diminished effect, nausea, vomiting, cardiac arrhythmias, and hypotension.
b. Carbidopa: Carbidopa, a dopamine decarboxylase inhibitor, diminishes the metabolism of levodopa in the periphery, thereby increasing the availability of levodopa to the CNS. So, The addition of carbidopa lowers the dose of levodopa
needed by four- to five-fold and, consequently, decreases the severity of adverse effects arising from peripherally formed dopamine.
