Table 1.

The timeline of significant events

L-dopa/carbidopa timeline
1958–1975: The Parkinson’s disease death rate decreased from 2.9/100,000 to 1.6/100,000 and was attributed to L-dopa.61
1967: The first four studies on the administration of a general decarboxylase inhibitor for the management of L-dopa-induced nausea were documented.86
1975: The original brand of L-dopa with carbidopa (Sinemet®) was approved by the US FDA.62,86
1976–2011: The Parkinson’s disease death rate increased by 328.7%.61,84
1977: The first paper demonstrating significant peripheral and central PLP depletion by carbidopa was submitted for publication.5
1999: Pharmaceutical companies discontinued distributing the prescription form of L-dopa (a single-ingredient drug leaving L-dopa/carbidopa combinations the only prescription options).87
2003: The CDC added Parkinson’s disease to the top 15 causes of death; it entered at number 14.6
2012: Paper that asserts that carbidopa irreversibly binds to PLP and PLP-dependent enzyme molecules was published. Prior to this, carbidopa depletion of PLP was viewed as a side event, not the mechanism of action.7

Abbreviations: L-dopa, L-3,4-dihydroxyphenylalanine; US FDA, United States Food and Drug Administration; PLP, pyridoxal 5′-phosphate; CDC, Centers for Disease Control and Prevention.