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• Are classified into the D1- and D2-like receptor subtypes (based on their molecular
structure and pharmacology
• D1-like receptors, composed of D1 and D5 receptors, stimulate adenylyl cyclase
activity,
• D2like receptors, composed of D2,D 3, and D4 receptors, inhibit adenylyl cyclase
activity and regulate/modulate the activity of several ion channels.
• In the early 1970s, receptors for neurotransmitters acting via second messengers had not been identified
biochemically nor were there definitive links to such messengers. The discovery by John W. Kebabian and Paul
Greengard of a dopamine-sensitive adenyl cyclase, accordingly, was a giant step forward. The investigators first
characterized the enzyme in sympathetic ganglia where in dopamine producing cells link pre- and post-synaptic
neurons. Then, in the corpus striatum, the brain area enriched in dopamine, they delineated the enzyme’s
properties and showed that it was inhibited by antipsychoticdrugs, leading to a large body of research on dopamine
as a mediator of antipsychotic drug action and putative roles for this transmitter in the pathophysiology of
schizophrenia.
THERE ARE FOUR MAJOR PATHWAYS FOR
THE DOPAMINERGIC SYSTEM IN THE
BRAIN:
• In which fibres originate from the substantia nigra (pars compacta) and project
rostrally to become widely distributed in the basal ganglia (caudate nucleus and
the putamen). In this pathway dopamine plays a significant role in movement
(the control of motor function and in learning new motor skills). Degeneration of
the nigrostriatal system causes Parkinson's disease.
• The extrapyramidal effects of antipsychotic drugs are thought to result from the
blockade of these striatal dopamine receptors .
2. THE MESOLIMBIC PATHWAY
• In which the dopaminergic fibers also arise from the A10 region (the ventral
tegmental area) and project to the frontal cortex and septohippocampal regions.
• Mesocortical dopamine mediates cognitive and emotional behaviour.
• Levels of dopamine in the brain, especially the prefrontal cortex, help in improved
working memory and attentions.
• However, this is a delicate balance and as levels increase or decrease to abnormal
levels, memory suffers. Antipsychotic drugs worsen negative symptoms of
schizophrenia by blocking dopamine receptors in the mesocortical pathway
4. THE TUBEROINFUNDIBULAR PATHWAY
• which originates in the arcuate nucleus ofthe hypothalamus (arcuate and
paraventricular nuclei) and projects to pituitary gland (the median eminence).
• Dopamine in this pathway inhibit prolactin release. Antipsychotic drugs that
block dopamine receptors in the pituitary may thus disinhibit prolactin
release and cause galactorrhea.
• Dopamine is the main neuroendocrine inhibitor of the secretion of prolactin
from the anterior pituitary gland.
• Dopamine is occasionally called prolactin-inhibiting factor (PIF), prolactin-
inhibiting hormone (PIH), or prolactostatin
• Dopamine became clinically relevant when Hornykiewicz discovered its depletion in the caudate nucleus
of patients with Parkinson’s disease, whereas i.v. administration of L-dihydroxyphenylalanine, the amino
acid precursor of dopamine, dramatically and rapidly alleviated Parkinsonian symptoms
• Neurotransmitter yang berperan dalam patofisiologinya adalah DA, 5HT, Glutamat,
peptide,norepinefrin (Price, 2006).
• Pada pasien skizoprenia terjadi hipereaktivitas system dopaminergik (hiperdopaminergia
pada sistem mesolimbik →berkaitan dengan gejala positif, dan hipodopaminergia pada
sistem mesocortis dan nigrostriatal→bertanggungjawab terhadap gejala negatif dan gejala
ekstrapiramidal)
• Reseptor dopamine yang terlibat adalah reseptor dopamine-2(D2) yang akan dijumpai
peningkatan densitas reseptor D2 pada jaringan otak pasien skizoprenia.
• Peningkatan aktivitas sistem dopaminergik pada sistem mesolimbik yang bertanggungjawab
terhadap gejala positif. Sedangkan peningkatan aktivitas serotonergik akan menurunkan
aktivitas dopaminergik pada sistem mesocortis yang bertanggung-jawab terhadap gejala
negatif.
CONCLUSION
1. Neurontrasmitter Dopamin memiliki prekursor yang sama dengan epinefrin dan norepinefrin yaitu L-
Thyrosin yang berasal dari hati.
2. Memiliki 2 tipe reseptor, D1 like reseptor & D2 like reseptor
3. Tubuh dapat optimal fungsinya bila terjadi keseimbangan neurontransmitter
4. Efek buruk dapat terjadi apabila produksi dopamin menurun seperti pada pasein parkinson yakni
terdapat defek pada substansia nigra sehingga aktivitas motoriknya mengalami gangguan.
5. Pada kondisi schizophrenia apabila kadar dopamin meningkat akan mengakibatkan timbulnya gejala
postif dan sebaliknya apabila kadar dopamin menurun akan mengakibatkan timbulnya gejala negatif.
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