Conversion to dopamine also occurs in the peripheral tissues, i.e. outside the brain. This may be the mechanism of the adverse effects of levodopa. It is standard clinical practice to co-administer a peripheral DOPA decarboxylase inhibitor—carbidopa or benserazide—and often a catechol-O-methyl transferase (COMT) inhibitor, to prevent synthesis of dopamine in peripheral tissue. Co-administration of pyridoxine without a decarboxylase inhibitor accelerates the extracerebral decarboxylation to such an extent that it cancels out the effects of levodopa administration, a circumstance which historically caused great confusion.
For those taking it as a supplement EGCG or green tea is a natural decarboxylase inhibitor.
Levodopa, co-administered with a peripheral DOPA decarboxylase inhibitor, has been tested as a possible treatment for restless leg syndrome (RLS).
Although there are many adverse effects associated with levodopa, particularly psychiatric ones, it has fewer than other anti-Parkinson's drugs, including anticholinergics, amantadine, and dopamine agonists.
More serious are the effects of chronic levodopa administration, which include:
Clinicians will try to avoid these by limiting levodopa dosages as far as possible until absolutely necessary.
Some studies suggest a cytotoxic role in the promotion and occurrence of adverse effects associated with levodopa treatment. Though the drug is generally safe in humans, some researchers have reported an increase in cytotoxicity markers in rat pheochromocytoma PC12 cell lines treated with levodopa. Other authors have attributed the observed toxic effects of levodopa in neural dopamine cell lines to enhanced formation of quinones through increased auto-oxidation and subsequent cell death in mesencephalic cell cultures. Though levodopa is generally considered safe, some controversy surrounds use of the drug in Parkinson's Disease given some data indicating a deleterious effect on intracellular and neuronal tissue involved in the pathogenesis of the disease.
L-DOPA is produced from the amino acid tyrosine by the enzyme tyrosine hydroxylase. It is also the precursor molecule for the catecholamine neurotransmitters dopamine and norepinephrine (noradrenaline), and the hormone epinephrine (adrenaline). Dopamine is formed by the decarboxylation of L-DOPA.
L-DOPA can be directly metabolized by catechol-O-methyl transferase (COMT) to 3-O-methyldopa (3-OMD) and then further to vanillactic acid (VLA). This metabolic pathway is non-existent in the healthy body but becomes important after peripheral L-DOPA administration in patients with Parkinson's Disease or in the rare cases of patients with aromatic L-amino acid decarboxylase (AADC) enzyme deficiency.
The 2001 Nobel Prize in Chemistry was also related to L-DOPA: the Nobel Committee awarded one-fourth of the prize to William S. Knowles for his work on chirally-catalysed hydrogenation reactions, the most noted example of which was used for the synthesis of L-DOPA.
L-DOPA at 500-1,000 mg will effectively raise HGH levels.
Role of L-DOPA in Spinal Nociceptive Reflex Activity: Higher Sensitivity of A[delta] Versus C Fibre-Evoked Nociceptive Reflexes to L-DOPA
Jul 01, 2011; Summary The role of L-dopa in spinal nociceptive reflex activity has been re-evaluated. In high spinal cats, with...
High performance microbiological transformation of L-tyrosine to L-dopa by Yarrowia lipolytica NRRL-143.(Research article)
Aug 16, 2007; Authors: Sikander Ali (corresponding author) ; Jeffry L Shultz ; Ikram-ul-Haq BackgroundThe yeast Yarrowia lipolytica is...