ABSTRACT
A revolution in the medical treatment of Parkinson’s disease (PD) occurred with the recognition that levodopa (3,4 dihydroxy-L-phenylalanine, Figure 64.1), the direct biochemical
precursor to dopamine (DA), replenishes neuronal DA stores and improves many of the motor features of PD. Since its introduction approximately 4 decades ago, levodopa remains the single most effective drug for alleviating the
Introduction ............................................................................................................................................................................... 847 Pharmacokinetics ...................................................................................................................................................................... 848 Pharmacodynamics ................................................................................................................................................................... 849 Other Formulations and Routes of Administration ................................................................................................................... 849 Levodopa Adverse Effects ........................................................................................................................................................ 850 Levodopa: Potential Toxicity .................................................................................................................................................... 850 Clinical Trials Assessing Levodopa InŸuence on PD Clinical Progression .............................................................................. 851 Levodopa Treatment and Functional Brain Imaging Studies .................................................................................................... 851 Delaying Levodopa Treatment .................................................................................................................................................. 851 Levodopa Dose Restriction ....................................................................................................................................................... 851 Initial Treatment: Levodopa versus DA Agonists ..................................................................................................................... 851 Initial Dosing of Levodopa ....................................................................................................................................................... 853
Immediate-Release Levodopa .............................................................................................................................................. 853 Sustained-Release Carbidopa/Levodopa .............................................................................................................................. 854 Initiation of Carbidopa/Levodopa with Entacapone? ........................................................................................................... 854
Motor Complications of Levodopa Therapy ............................................................................................................................. 855 Dyskinesia ............................................................................................................................................................................ 855 Proposed Mechanisms of Levodopa-Induced Dyskinesia ................................................................................................... 855 Clinical Features and Treatment of Dyskinesia ................................................................................................................... 856
Peak-Dose Dyskinesia ..................................................................................................................................................... 856 Biphasic Dyskinesia (D-I-D) ........................................................................................................................................... 856
Motor Fluctuations ............................................................................................................................................................... 856 Recognition of the Short-Duration Response .................................................................................................................. 857 Treatment of Short-Duration Levodopa Responses ........................................................................................................ 857
Freezing ................................................................................................................................................................................ 857 Functional Neurosurgery and Levodopa .............................................................................................................................. 857
Nonmotor Features of PD and Levodopa.................................................................................................................................. 857 Insomnia ............................................................................................................................................................................... 858 Anxiety, Akathisia, and Panic .............................................................................................................................................. 858 Pain and Paresthesias ........................................................................................................................................................... 858 Dyspnea ................................................................................................................................................................................ 858
Levodopa and Elevated Plasma Homocysteine ......................................................................................................................... 859 Levodopa and Risk of Melanoma ............................................................................................................................................. 859 Summary ................................................................................................................................................................................... 859 References ................................................................................................................................................................................. 859
motor symptoms of PD and is the only drug documented to improve life span in this progressive disorder [1-7].
