Corpus dopamine depletion

High doses of reserpine characteristically produce sedation, lassitude, nightmares, and severe mental depression occasionally, these occur even in patients receiving low doses (0.25 mg/d). Much less frequently, ordinary low doses of reserpine produce extrapyramidal effects resembling Parkinson s disease, probably as a result of dopamine depletion in the corpus striatum. Although these central effects are uncommon, it should be stressed that they may occur at any time, even after months of uneventful treatment. Patients with a history of mental depression should not receive reserpine, and the drug should be stopped if depression appears. 

Txvo balanced systems are important in the extrapyramidal control of motor activity at the level of the corpus striatum and substantia nigra in one the neurotransmitter is acetylcholine in the other it is a dopamine. In Parkinson s disease there is degenerative loss of nigrostriatal dopaminergic neurons and the sjunptoms and signs of the disease are due to dopamine depletion. 

The symptoms of extrapyramidal involvement which accompany treatment by many of the psychotropic drugs are generally described as Parkinsonian . Although the symptoms respond to treatment by anti-Parkinsonian drugs, they cannot be attributed either to dopamine deficiency or to acetylcholine excess. Thus, the extent of the spasticity produced in cats by chlorpromazine, prochlorperazine and mepazine bears no relation to the degree of dopamine depletion in the corpus striatum . Neither chlorpromazine nor reserpine have a marked effect on the acetylcholine content of brain nor do they alter the proportion of free ester . 

FIGURE 29-1. Anatomy of the extrapyramidal system. The extrapyramidal motor system controls muscle movement through a system of pathways and nerve tracts that connect the cerebral cortex, basal ganglia, thalamus, cerebellum, reticular formation, and spinal neurons. Patients with Parkinson s disease have a loss of dopamine neurons in the substantia nigra in the brain stem that leads to depletion of dopamine in the corpus striatum. The corpus striatum is made up of the caudate nucleus and the lentiform nuclei that are made up of the putamen and the globus pallidus. 

Recently we have been working on Parkinson s disease. This and other similar diseases are due to a depletion of dopamine in the corpus striatum. Direct addition of dopamine is not effective in the treatment presumably because it does not cross the blood-brain barrier. However, levodopa, the metabolic precursor of dopamine, does cross the blood brain barrier and is believed to then be converted to dopamine in the basal ganglia. 

The mechanism of the neurological symptoms in Parkinson s disease was discovered from the ability of reserpine to cause akinesia in humans by the depletion of central catecholamine stores. The dopamine levels in patients who died from parkinsonism were found to be extremely low because of deterioration of the dopaminergic neuronal cell bodies and the pathways connecting the substantia nigra with the corpus striatum. 

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