Dopamine L-dopa

The immediate metabolic precursor to dopamine, l-DOPA (L-dihydroxphenylalanine) is converted to the active neurotransmitter dopamine by the action of the enzyme aromatic amine acid decarboxylase (AADC). l-DOPA (INN name Levodopa) is the main diug used to treat Parkinson s disease. 

These symptoms are alleviated by administering levodopa (L-dopa), a precursor for dopamine. L-dopa is taken up by the axon terminals of dopaminergic neurons and used to form dopamine. Interestingly, in some patients, a side effect of dopamine replacement therapy is the development of symptoms characteristic of schizophrenia. (Recall that this mental disorder is caused by overactive dopaminergic neurons.) On the other hand, drugs used to treat schizophrenia — dopamine receptor antagonists — may elicit symptoms of Parkinson s disease. 

Dopamine activity can be enhanced in one of four main ways. Medications can stimulate dopaminergic nerve cells to release dopamine into the synapse. This is the way that stimulants such as methylphenidate (Ritalin), dextroamphetamine (Dexe-drine), and dextroamphetamine/amphetamine (Adderall) work. In addition, certain drugs of abuse, notably cocaine and methamphetamine, act in part in this way. Providing more of the raw material that nerve cells use to manufacture dopamine can also increase dopamine activity. This is the approach that neurologists use when they prescribe L-DOPA (Sinemet) to patients with Parkinson s disease. Nerve cells convert L-DOPA into dopamine. L-DOPA otherwise has little place in the treatment of psychiatric disorders. Dopamine activity can also be increased by medications that directly stimulate dopamine receptors. Bromocriptine, another medication used to... 

Dopamine does not penetrate the blood-brain barrier. L-Dopa is actively transported into the brain and then converted to dopamine. L-Dopa is rapidly metabolized and only about 1% of an oral dose reaches the brain. In the current... 

Fig. 6.2.3a-c AADC assay using HPLC and EC detection of dopamine, a Standard mixture b serum control sample c serum AADC deficiency. DA Dopamine, L-Dopa 3,4-dihydroxy-l-phenylalanine... 

Electrochemical oxidation of some catecholamines such as dopamine, L-dopa, and methyldopa has been studied using cyclic voltammetry. The catecholamines undergo intramolecular cyclization to form the corresponding o-quinone derivatives. The significant differences in the electrochemical behaviour of the catecholamines have been attributed to the effects of the side-chain carboxyl group.253 Electron-transfer reactions of 2,-deoxyguanosine-5,-monophosphate (dGMP) in phosphate buffers by cyclic... 

Dopamine s role in the coordination of movement can be partially understood by examining Parkinson s disease. This illness is associated with low levels of dopamine in the brain and is characterized by spastic motion of the eyelids as well as rhythmic tremors of the hands and other parts of the body. One method of treating Parkinson s disease is to increase the concentration of dopamine in the brain. This is most effectively accomplished by administering the precursor of dopamine, L-dopa. In order to prevent concentrations of norepinephrine from increasing as well, L-dopa is given in conjunction with a drug that inhibits norepinephrine synthesis. 

Q6 Dopamine is unable to cross the blood-brain barrier and so cannot enter the brain. A precursor of dopamine, L-dopa, which can penetrate the blood-brain barrier, is given instead (see above). 

In Parkinson disease, Oleg Homykiewitz examined autopsy material from 180 patients and found a huge deficit of dopamine in the basal ganglia. Existing therapy, which is a successful symptom treatment, is to replace this deficit by giving a precursor to the dopamine, L-DOPA. The L-DOPA is converted by the brain into dopamine. Alternatively, one can make artificial dopamines, that is, dopamine receptor agonists, which have a very similar effect on the receptor as natural dopamine. 

The dopamine deficiency hypothesis of Parkinson s disease led to new treatment approaches involving the administration of L-dopa, a precursor of dopamine. L-dopa was administered to patients in hopes of correcting the dopamine deficiency and proved to be dramatically effective in relieving the symptoms of this disease. Dopamine itself is not effective because it does not enter the brain from the bloodstream. The brain is protected from toxic compounds that might enter... 

A considerable pool of autoxidizable compounds such as dopamine, L-dopa, and noradrenalin [4]... 

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