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Pathway Description
Levodopa Pahway
Homo sapiens
Drug Action Pathway
Created: 2021-07-28
Last Updated: 2023-10-25
Levodopa is a dopamine precursor used in the management of Parkinson's disease, often in combination with carbidopa, as well as other conditions associated with parkinsonism. Degeneration of the dopaminergic neurons in substantia nigra occurs in patients with Parkinson's disease. This condition results in the disruption of the nigrostriatal pathway and thus, decreasing the striatal dopamine levels. Parkinsonism is a hypokinetic disorder, which causes decreased motor output. The goal of levodopa is to increase dopamine in the striatum to increase and improve motor output.
Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine via the enzyme aromatic-L-amino acid decarboxylase. The dopamine is then transported into vesicles via vesicular monoamine transporter-2. When an action potential is generated and reaches the nerve terminal where dopamine is secreted into the synapse by exocytosis. The dopamine activated D2 receptors on the post-synaptic receptor, which activates the Gi signaling cascade and inhibits the neurons leaving the striatum and going to the external globus pallidus. Relieving the inhibition of the external globus pallidus allows the external globus pallidus to inhibit the subthalamic nucleus, internal globus pallidus and the substantia nigra pars reticulata. Therefore, the subthalamic nucleus is unable to activate the internal globus pallidus and the substantia nigra pars reticulata and the internal globus pallidus and the substantia nigra pars reticulata cannot inhibit the thalamus. Since the thalamus is responsible for stimulating the cortex to produce motor output, this effect ultimately activates ultimately activates the cortex and increase motor output. Common adverse effects of Levodopa treatment are nausea, dizziness, headache, and somnolence. People on levodopa for long periods may also develop dyskinesia.
References
Levodopa Pahway References
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