Phenylalanine Levodopa

MH van Woert. Phenylalanine and tyrosine metabolism in Parkinson s disease treated with levodopa. Clin Pharmacol Ther 12 368-375, 1971. 

Cyclization adrenaline azathioprine calciferol chlordiazepoxide cholecalciferol clomiphene hydroxychloroquine levodopa methotrexate phenylalanine tyrosine... 

L-Dopa. Dopamine itself cannot penetrate the blood-brain barrier however, its natural precursor, L-dihydroxy-phenylalanine (levodopa), is effective in replenishing striatal dopamine levels, because it is transported across the blood-brain barrier via an amino acid carrier and is subsequently decarboxy-lated by DOPA-decarboxylase, present in striatal tissue. Decarboxylation also takes place in peripheral organs where dopamine is not needed, likely causing undesirable effects (tachycardia, arrhythmias resulting from activation of Pi-adrenoceptors [p. 114], hypotension, and vomiting). Extracerebral production of dopamine can be prevented by inhibitors of DOPA-decarboxylase (car-bidopa, benserazide) that do not penetrate the blood-brain barrier, leaving intracerebral decarboxylation unaffected. Excessive elevation of brain dopamine levels may lead to undesirable reactions, such as involuntary movements (dyskinesias) and mental disturbances. 

Entacapone and tolcapon are selective and reversible catechol-O-methyltransferase (COMT) inhibitors which also inhibit the break down of levodopa to 3-methoxy-4-hydroxy-L-phenylalanine. 

There are instances in which toxicants have chemical or structural similarities to endogenous chemicals that rely on these special transport mechanisms for normal physiological uptake and can thus utilize the same system for membrane transport. Useful examples of drugs known to be transported by this mechanism include levodopa, which is used in treating Parkinson s disease, and fluorouracil, a cytotoxic drug. Levodopa is taken up by the carrier that normally transports phenylalanine, and fluorouracil is transported by the system that carries the natural pyrimidines, thymine, and uracil. Iron is absorbed by a specific carrier in the mucosal cells of the jejunum, and calcium by a vitamin D-dependent carrier system. Lead may be more quickly moved by a transport system that is normally involved in the uptake of calcium. 

Hypertensive crisis A/ith headache, intracranial bleeding, and death may result from combining MAO inhibitors with sympathomimetic drugs (e.g., amphetamines, methylphenidate, cocaine, dopamine, epinephrine, norepinephrine, and related compounds methyidopa, levodopa, L-tryptophan, L-tyrosine, and phenylalanine)... 

DL-Dopa may be first prepared from vanilline and glycine which is then converted to the DL-N-acetyl-3-methoxy-4-acetoxy phenylalanine. The resulting product is then resolved by means of a-phe-nyl-ethyl amine which upon hydrolysis with aqueous HBr forms levodopa. 

A study found that the clinical response to a constant intravenous infusion of levodopa in 4 patients was unchanged by glycine and tysine but was reduced by phenylalanine, leucine and isoleucine, although the plasma levodopa levels remained unchanged. ... 

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