Parkinson's disease: carbidopa, nausea, and dyskinesia

Abstract

When l-dopa use began in the early 1960s for the treatment of Parkinson’s disease, nausea and reversible dyskinesias were experienced as continuing side effects. Carbidopa or benserazide was added to l-dopa in 1975 solely to control nausea. Subsequent to the increasing use of carbidopa has been the recognition of irreversible dyskinesias, which have automatically been attributed to l-dopa. The research into the etiology of these phenomena has identified the causative agent of the irreversible dyskinesias as carbidopa, not l-dopa. The mechanism of action of the carbidopa and benserazide causes irreversible binding and inactivation of vitamin B6 throughout the body. The consequences of this action are enormous, interfering with over 300 enzyme and protein functions. This has the ability to induce previously undocumented profound antihistamine dyskinesias, which have been wrongly attributed to l-dopa and may be perceived as irreversible if proper corrective action is not taken.

Parkinson’s disease managing reversible neurodegeneration

“…A relative nutritional deficiency (RND) occurs when an optimal diet does not meet nutritional requirements. 5 – 11 This paper demonstrates how the reversible PD symptoms induced by newly identified RNDs have been allowed to accumulate because of the disease process or traditional treatment. These symptoms have traditionally been exclusively attributed to irreversible PN.…”

“…In PD patients, reversible RNDs may induce PD symptoms which may be inappropriately managed when treated as PN. 9 – 11 Figure 1 illustrates 29 primary system depletions associated with PD and its treatment. Each depletion induces and represents a significant underlying RND which contributes to PD symptom exacerbation and/or overall irreversible disease collapse.…”

“… 33 , 34 , 38 – 40 Carbidopa-associated vitamin B6 depletion. 10 , 11 , 41 , 42 Carbidopa associated serotonin depletion. 43 , 44 Carbidopa-associated dopamine depletion.…”

“…45 , 46 Carbidopa-associated vitamin B6 depletion. 10 , 11 , 41 , 42 Vitamin B6 depletion may deplete glutathione. 45 , 46 Glutathione depletion may deplete S-adenosylmethionine.…”

Study of the Activity and Possible Mechanism of Action of a Reversible Inhibitor of Recombinant Human KAT-2: A Promising Lead in Neurodegenerative and Cognitive Disorders

“…Moreover, Schwarcz and others have recently shown the superior application of the reversible inhibition by using BFF-816 in preclinical trials [20]. It is noteworthy that the irreversible inhibition of PLP (active form of vitamin B 6 ) has a range of potential undesirable and dangerous side effects due the interference with the activity of over 300 PLP-dependent enzymes and proteins [21]. It is not far from the reality to state that nearly every major biological system in the human body could be affected directly or indirectly by the inactivation of PLP which is needed in more than 140 different enzymatic pathways [22].…”