Dopamine receptor D3
Encyclopedia
D dopamine receptor is a protein
that in humans is encoded by the DRD3 gene
.
This gene encodes the D3 subtype of the dopamine receptor
. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that this receptor plays a role in cognitive and emotional functions. It is a target for drugs which treat schizophrenia
, drug addiction, and Parkinson's disease
. Alternative splicing of this gene results in multiple transcript variants that would encode different isoforms, although some variants may be subject to nonsense-mediated decay (NMD).
D3 agonists like 7-OH-DPAT
, pramipexole
, and rotigotine
, among others, display antidepressant
effects in rodent models of depression.
such as pramipexole
and ropinirole
, but these also bind to D2 and lack the strong receptor type and subtype selectivity that some of the following research compounds afford:
with CLIC6
and EPB41L1
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the DRD3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
This gene encodes the D3 subtype of the dopamine receptor
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that this receptor plays a role in cognitive and emotional functions. It is a target for drugs which treat schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, drug addiction, and Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. Alternative splicing of this gene results in multiple transcript variants that would encode different isoforms, although some variants may be subject to nonsense-mediated decay (NMD).
D3 agonists like 7-OH-DPAT
7-OH-DPAT
7-OH-DPAT is a synthetic compound that acts as a dopamine receptor agonist with reasonable selectivity for the D3 receptor subtype, and low affinity for serotonin receptors, unlike its structural isomer 8-OH-DPAT....
, pramipexole
Pramipexole
Pramipexole is a non-ergoline dopamine agonist indicated for treating early-stage Parkinson's disease and restless legs syndrome...
, and rotigotine
Rotigotine
Rotigotine is a non-ergoline dopamine agonist indicated for the treatment of Parkinson's disease and restless legs syndrome in Europe and the United States...
, among others, display antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
effects in rodent models of depression.
Ligands
Numerous non-selective prescription drugs bind to the D3 receptor, notably including some of the newer dopamine agonists used for Parkinson's diseaseParkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
such as pramipexole
Pramipexole
Pramipexole is a non-ergoline dopamine agonist indicated for treating early-stage Parkinson's disease and restless legs syndrome...
and ropinirole
Ropinirole
Ropinirole is a non-ergoline dopamine agonist. It is manufactured by GlaxoSmithKline , Cipla and Sun Pharmaceutical. It is used in the treatment of Parkinson's disease...
, but these also bind to D2 and lack the strong receptor type and subtype selectivity that some of the following research compounds afford:
Agonists
- 8-OH-PBZI8-OH-PBZI8-OH-PBZI is a drug used in scientific research which acts as a potent and selective agonist for the dopamine D3 receptor....
(cis-8-Hydroxy-3-(n-propyl)-1,2,3a,4,5,9b-hexahydro-1H-benz[e]indole) - PF-219,061PF-219,061PF-219,061 is a drug developed by Pfizer which acts as a potent and highly selective agonist for the dopamine D3 receptor. It is under development as a potential medication for the treatment of female sexual dysfunction.-See also:* ABT-670* ABT-724...
((R)-3-(4-Propylmorpholin-2-yl)phenol): >1000-fold functional (efficiacy) selectivity over D2 - compound R,R-16: 250x binding selectivity over D2
- trans-N-{4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]cyclohexyl}-3-methoxybenzamide, full agonist, > 200-fold binding selectivity over D4, D2, 5-HT1A5-HT1A receptorThe 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...
, and α1-receptorsAlpha-1 adrenergic receptorThe alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic... - (-)-7-{[2-(4-Phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol
- BP-897: partial agonist
- FAUC 73
- FAUC 460: partial agonist, outstanding affinity and selectivity
- FAUC 346: partial agonist, subtype selective
- PD-128,907PD-128,907PD-128,907 is a drug used in scientific research which acts as a potent and selective agonist for the dopamine D2 and D3 receptors. It is used for studying the role of these receptors in the brain, in roles such as inhibitory autoreceptors that act to limit further dopamine release, as well as...
- compound 12: partial agonist, Ki = 0.41nM, 800x binding selectivity over D2
- piribedilPiribedilPiribedil is an antiparkinsonian agent and piperazine derivative which acts as a D2 and D3 receptor agonist...
Antagonists
- FAUC 365, silent antagonistReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
, subtype selective - compound 29
- NafadotrideNafadotrideNafadotride is a dopamine antagonist with reasonable selectivity for the D3 subtype ....
- NGB-2904
- SB-277011-ASB-277011-ASB-277,011A is a drug which acts as a potent and selective dopamine D3 receptor antagonist, which is around 80-100x selective for D3 over D2, and lacks any partial agonist activity....
, selective D3 antagonist, 80x selectivity over D2 with no partial agonist effects, used in drug addiction research as a potential therapy for addiction to several different drugs - DomperidoneDomperidoneDomperidone is an antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally, rectally or intravenously, generally to suppress nausea and vomiting, or as a prokinetic agent...
- D2 and D3 antagonist
Interactions
Dopamine receptor D3 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with CLIC6
CLIC6
Chloride intracellular channel protein 6 is a protein that in humans is encoded by the CLIC6 gene.-Interactions:CLIC6 has been shown to interact with Dopamine receptor D3....
and EPB41L1
EPB41L1
Band 4.1-like protein 1 is a protein that in humans is encoded by the EPB41L1 gene.-Interactions:EPB41L1 has been shown to interact with ITPR1, Dopamine receptor D2, Dopamine receptor D3, CENTG1 and Nuclear mitotic apparatus protein 1....
.