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DOPAMIN
A dopaminerg neurotranszmisszio
egyszeru semaja
A dopaminerg axon terminalis
Left picture shows rich
presence of dopaminecontaining nerve endings
(green dots) in the basal
ganglia of a rat brain,
visualized by fluorescence
microscopy. To the right, a
close-up of one nerve ending
as seen in the electron
microscope. The black dots
in the vesicles represent
stored dopamine.
A dopamin receptorok
szignaltranszdukcioja
Az adenil-ciklázt befolyasolo
dopamin receptorok (D1, D5, D2)
Dopamin metabolitok
Agytörzsi magvak
Limbikus kéreg
HO
HO
CH2 CH2 NH2
MAO
Nigro-striatalis pályák!
HO
O
HO
HOMOVANILINSAV:
Szintje a dopaminerg
neuronok funkcionális
állapotara utal
Parkinson kór 
Schizophrenia 
CH2 C
H
3,4-dihydroxy phenylacetaldehyde
DOPAC
Aldehyde dehydrogenase
HO
HO
CH2 COOH
COMT
MeO
HO
CH2 COOH
Homovanillic acid
A dopaminerg rendszer kóros
működése következtében kialakuló
betegségek:
Parkinson kór
Schizophrenia
Dopaminergic pathways of the human brain in normal condition (left)
and Parkinson's disease (right). Red Arrows indicate suppression of the
target, blue arrows indicate stimulation of target structure.
A Parkinson kór indukalasa
*Cycad tree - trópusi gyom
B-N-metil-amino-alanin (BMAA)
*1-metil-4-phenyl-1,2,3,3tetrahidropiridin (MPTP)
iv. kábítószerrel
(heroin-származék szintézise során
keletkezik)
A dopaminerg neuronok felveszik
↓ MAO-B
1-metil-4-fenil pyridinium (MPP+)
→ toxikus
*Complex I gatlok – (peszticidek,
rotenon)
A Parkinson kor terapiaja
*L-DOPA (levodopa)
Periferiás DOPAdekarboxiláz aktivitas 1 %
kerül az agyba
Kombináció:Carbidopa
(DOPA-dekarboxiláz gátló,
agy-vér gáton nem jut át,
csak a periferian gatol)
* Dopamin receptor
agonisták
(schizophrenia!)
Schizophrenia
Egyik elképzelés:
Centrális dopaminerg neuronok fokozott aktivitása
Hatékony antipsychotikus szerek:
Dopamin receptor gátlók – D2 receptor gatlo neuroleptikumok
(Parkinson kór alakulhat ki!)
• Dopamin szint az agyban emelkedett
• Homovanilinsav szint a liquorban emelkedett
• D2 receptorok száma megnőtt
USA lakosság 1 %-a érintett
Kórházi ágyak 25 %-at ilyen betegek foglalják el
Some properties of dopamine receptors. New receptors, isolated
using appropriate probes and genomic or cDNA libraries, are
being reported frequently
• At least five different major classes are recognized (D1D5), with some subtypes formed by alternative splicing.
• They are membrane proteins, at least some of which are
glycosylated.
• Most have seven transmembrane domains with
cytoplasmic loops.
• Most appear to be coupled to G proteins.
• Some are positively coupled to adenylyl cyclase (eg, D1),
• at least one (D2) negatively.
• At least one subtype (of D1) appears to be coupled to
phospholipase C.
Some properties of dopamine receptors. New receptors, isolated
using appropriate probes and genomic or cDNA libraries, are
being reported frequently
• Five distinct subtypes of the D4 receptor have been
recognized, it being the first member of the catecholamine
family of receptors to show polymorphic variation in the
human population.
Based on
Strange PG: Interesting times for dopamine receptors.
Trends Neurol Sci 1991;14:43, and Iversen L: Which D4
do you have? Nature 1992;358:109.
Some properties of dopamine receptors. New receptors, isolated
using appropriate probes and genomic or cDNA libraries, are
being reported frequently
• Some, at least, are regulated by phosphorylation.
• Drug affinities of most neuroleptics for the D2 receptor
reflect their potencies in treating schizophrenia.
• The various receptors show different anatomic
distributions.
• The D4 receptor binds the atypical neuroleptic clozapine
with an affinity ten times higher than that of D2 sites.