L-Dopa+vs.+D-Dopa

__Parkinsonian Treatments and L-Dopa vs. D-Dopa__

Dopamine, a chemical molecule which derives its name from an amine group attached to a //d//ihydr//o//xy//p//henyl//a//lanine (dopa-amine), is a neurotransmitter produced in the substantia nigra and the ventral tegmental area of the brain.

The main role of dopamine is in reward- driven learning. Every time the brain experiences a reward, the dopamine levels in the brain elevate (Yavich, 2007). This also comes in to play with addiction. Many addictive drugs, act directly on the dopamine system—thus, when a person “gets high”, they feel rewarded for their actions, and therefore, continue to take the drug. Dopamine is the key neurotransmitter affected in Parkinson’s disease—a degenerative disorder that causes tremor and motor impairment. This degeneration is caused by the loss of dopamine-secreting neurons in the substantia nigra.

Common treatments of Parkinson’s have been the use of the levodextrorotary form of dopamine, otherwise known as L-Dopa (L-3,4-dihydroxyphenylalanine). This is the precursor to dopamine. It is given to Parkinsonian suffers in order to increase dopamine concentrations in the brain; however, initially it was believed to be a biologically inactive molecule.

A study done by O. Hornykiewicz from the University of Vienna declared this to be false. Interest was sparked in the L-dopa molecule after a discovery in 1938 that L-dopa was enzymatically converted to dopamine in the animal and human body (Hornykiewicz, 2002). By the 1960s, it was determined that L-dopa was a successful treatment for those suffering with Parkinson’s Disease.

Dextrodopa (D-3,4-dihydroxyphenylalanine), or D-Dopa, has the opposite chirality of L-Dopa, and it too was initially believed to be biologically inactive. However, it was found in 1988 in a study conducted by Karoum, Freed, Chuang, Cannon-Spoor, Wyatt, and Costa that rats with lesions in their substantia nigra and also injected with D-dopa in combination with carbidopa, increased dopamine concentration in the striatum to the same concentration as a similar treatment as L- Dopa plus carbidopa. It was found that although there were no true dopamine concentrations in the lesioned striata area, there was a significant increase in dopamine metabolites, which concludes that some form of extraneuronal form of dopamine was present. This suggest that D-Dopa can be converted to dopamine in a striatum that is devoid of dopamine nerve terminals, and that D- and L-Dopa produced a change in dopamine levels with similar efficacy. This turning behavior was attributed to the stimulation of sensitive dopamine receptors in the lesioned striata by the extraneuronally formed dopamine. D-Dopa was converted to dopamine via transamination and/or D-amino acid oxidation to the 3,4-dihydroxyphenylalanine form.

It was noted in the study that D-Dopa onset of turning was delayed as compared with L-Dopa. This slow onset result suggests that the use of racemic mixture of DOPA combined with a peripheral dopadecarboxylase inhibitor may be more effective in the treatmen of Parkinson’s Disease as opposed to L- or D-dopa alone.

Resources: Hornykiewicz, O. 2002. “L-DOPA: from a biologically inactive amino acid to a successful therapeutic agent” //Amino Acids//. 23 (1-3): 65-70. Karoum F., Freed WJ., Chuang LW., Cannon-Spoor E., Wyatt RJ., Costa E. 1988. “D-Dopa and L-Dopa Similarly Elevate Brain Dopamine and Produce Turning Behavior in Rats.” //Brain Res.// 440(1):190 Yavich, L., Forsberg, M. M., Karayiorgou, M., Gogos J.A., Mannisto, P. T. Sept. 2007. “Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsa l Striatum”. //The Journal of Neuroscience//. 27(38): 10196 - 10209


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