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- Dopamine, a catecholamine, is synthesized in the terminal of dopaminergic neurons from tyrosine; the rate limiting step in the synthesis of dopamine is the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA a.k.a. levodopa) by the enzyme tyrosine hydroxylase which is present within the neuron; levodopa is converted rapidly to dopamine by aromatic L-amino acid decarboxylase; this process is blocked by reserpine (which also blocks synthesis and storage of norepinepherine) and leads to the depletion of dopamine; dopamine is metabolized my monoamine oxidase and is broken down to homovanillic acid
- Levodopa is the most effective agent in the treatment of Parkinson's disease; dopamine is not effective when given orally or IV because it cannot cross the blood-brain barrier; Levodopa is taken up by nigral cells which convert it to dopamine
- Adverse effects are due to the decarboxylation of levodopa to dopamine (half life is 1-3 hours); levodopa is usually administered with an inhibitor of aromatic L-amino acid decarboxylase such as carbidopa or benserazide (carbidopa + levodopa = sinamet); aromatic amino acid decarboxylase inhibitors decrease the peripheral metabolism of L-Dopa, reduce the amount of L-dopa needed, and increase the transport of L-dopa in the brain
- Levodopa can improve tremor, rigidity and bradykinesia
- On-off phenomenon in Parkinson disease refers to the random symptomatic fluctuations that patients have
- Adverse effects of dopamine include nausea and dyskinesias which are most common, also causes hallucinations and confusion in the elderly
- L-DOPA has been found to be toxic for dopaminergic and non-dopaminergic mesencephalic neurons in vitro; catechol-O-methyltransferase (COMT)attenuates toxicity.