Besides the central nervous system, L-DOPA is also converted into dopamine from within the peripheral nervous system. The resulting hyperdopaminergia causes many of the adverse side effects seen with sole L-DOPA administration. To bypass these effects, it is standard clinical practice to co-administer (with L-DOPA) a peripheral DOPA decarboxylase inhibitor (DDCI) such as carbidopa (medicines combining L-DOPA and carbidopa are branded as Lodosyn, Sinemet, Parcopa, Atamet, Stalevo) or with a benserazide (combination medicines are branded Madopar, Prolopa), to prevent the peripheral synthesis of dopamine from L-DOPA. Co-administration of pyridoxine without a DDCI accelerates the peripheral decarboxylation of L-DOPA to such an extent that it negates the effects of L-DOPA administration, a phenomenon that historically caused great confusion.

In addition, L-DOPA, co-administered with a peripheral DDCI, has been investigated as a potential treatment for restless leg syndrome. However, studies have demonstrated "no clear picture of reduced symptoms".[1]

The two types of response seen with administration of L-DOPA are:

Short-duration response, which is related to the half-life of the drug

Longer-duration response, which depends on the accumulation of effects over at least two weeks. This response is evident only in early therapy, as the inability of the brain to store dopamine is not yet a concern.

Biological role

Biosynthesis of dopamine

L-L-tyrosine by the enzyme tyrosine hydroxylase (TH). It is also the precursor for the monoamine or catecholamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of L-DOPA.

Clinicians will try to avoid these side effects by limiting L-DOPA doses as much as possible until absolutely necessary.

Possible overdose symptoms

Some test tube studies suggest a cytotoxic role in the promotion and occurrence of adverse effects associated with L-DOPA treatment.[5] 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 L-DOPA.[6] Other authors have attributed the observed toxic effects of L-DOPA in neural dopamine cell lines to enhanced formation of quinones through increased auto-oxidation and subsequent cell death in mesencephalic cell cultures.[7][8] There is no evidence of neurotoxicity in patients with Parkinson's Disease and it is generally considered safe, but some controversy surrounds its use in the treatment of Parkinson's Disease, given some test tube data indicate a deleterious effect on intracellular and neuronal tissue involved in the pathogenesis of the disease.[9]

Marine adhesion

L-DOPA is a key compound in the formation of marineadhesiveproteins, such as those found in mussels. It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. L-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.[11]