Ldopa and parkinsonian syndrome

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The Parkinsonian syndrome has long held the interest of psychologists, psychiatrists, and other behavioral investigators. Lately, the field of cerebral monoamines has received increased attention; first with the serotonin hypothesis of Brodie, then the noradrenaline hypothesis of Schildrant, in relation to neuron function, is receiving particular attention. (67). Dopamine is postulated to be the key neurotransmitter responsible for the origin of human intelligence (67). Dopamine, the direct precursor for noradrenaline, has a specific distribution pattern within the brain (Figure 9.3). It is concentrated mainly in the striatum and substantia nigra. It is deficient in patients with Parkinson's diseases (PD). l-DOPA has been studied as a treatment for neurological disorders such as Parkinson's disease (68,69).

Parkinson's disease is a common neurological disorder, affecting 1% of the people over the age of 60 years; it is a disease with the signs of rigidity, resting tremor, postural instability, which is due to underproduction of the neurotransmitter dopamine (DA) (70). One of the factors leading to PD is the marked loss of melanized nigrostriatal dopamine neurons, one of the principal components responsible for the normal control of movement. Signs of PD do not appear until a large majority of the nigrostriatal DA neurons have been damaged. Another factor that may mitigate the loss of nigrostriatal DA neurons in PD is a reduced rate of DA activation (71). Also, mitochondrial swelling was noticed as a result of low concentrations of DA, causing a mitochondrial damage triggering neurodegenerative process and PD (72). DA receptors are expressed not only in the central nervous system (CNS), but also in several peripheral tissues including arteries, heart, thymus, and peripheral blood lymphocytes (73). Unconjugated DA represents only 20-40% of the total DA excreted in human urine, with the remainder being mainly excreted in the form of phenolic sulfate (74). It has been suggested that a low level of DA excretion is associated with hypokinesia and normal or excess rate of excretion with hyperkinesia and associated renal dysfunction (74). Overproduction of this catecholamine appears to be associated with the psychological disorder schizophrenia (68).

Introduction of l-DOPA has improved the clinical status of patients with Parkinson's disease (75). Levodopa (l-DOPA — synonym: levo-dihydroxyphenylalanine) therapy in Parkinson's disease was initiated after the suggestion of the role of dopamine in the neuronal system (71,76-81). Dopamine is also known to have a role in renal function, through its action on renal dopaminergic receptors and improved concentration of intrarenal area is dependent on l-DOPA availability (82). The biosynthesis dopamine is considered to start from tyrosine. obtained from dietary sources (82) (Figure 9.3). Blood borne tyrosine is taken into the brain to effect the functioning of dopaminergic neurons. When tyrosine has entered the neurons, l-DOPA (dihydoxyphenylalanine) is made using the cytsolic enzyme tyrosine hydroxylase (71). Subsequently, another cytosolic enzyme aromatic amino acid decarboxylase converts l-DOPA to dopamine (71). In the neurons, striatum is one of the main components of basal ganglia that are responsible for normal control of movement and role of dopamine is essential for this action (71). In Parkinson's disease, the importance of dopamine for striatum is clear due to the motor abnormalities seen in patients, which is characterized by a marked loss of melanized nigrostriatal dopamine neurons (71). Dopamine release in the striatum modulates activity in direct and indirect circuits, which are important for voluntary control of movement (71). Signs of Parkinson's

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