Dopamine receptor D₃ is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''DRD3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. This gene encodes the D₃ subtype of the

dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...

. The D₃ subtype inhibits

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

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 is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

drug addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...

, and

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

. 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 Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that exists in all eukaryotes. Its main function is to reduce errors in gene expression by eliminating mRNA transcripts that contain premature stop codons. Translation of these aberrant ...

(NMD).

Function

Alpha-synuclein (α-Syn) aggregation via Lewy bodies inclusion, a pathogenic signature exclusively present in PD patients, is decreased by D3 agonists while DA content is elevated by inhibiting DA reuptake and breakdown. The regulation of α-Syn aggregation and clearance enhances brain-derived neurotrophic factor (BDNF) secretion, which ultimately ameliorates neuroinflammation and oxidative stress while promoting neurogenesis and interacting with other DA receptors. D₃ agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...

effects in rodent models of depression.Apomorphine has the ability to help PD patients with their cognition awareness. In addition to having antidepressant properties such as regulating the depression-like behaviors and depression development, pramipexole has the capability to prevent and slow down cell apoptosis as well as to restore damaged neural networks and connections while rotigotine help PD patients to attenuates hyperpyrexia syndrome and schizophrenia.

Animal studies

D₃ agonists have been shown to disrupt prepulse inhibition of startle (PPI), a cross-species measure that recapitulates deficits in sensorimotor gating in neuropsychiatric disorders such as schizophrenia. In contrast, D3-preferring antagonists have antipsychotic-like profiles in measures of PPI in rats.

Ligands

Agonists

* ''trans-N''--3-methoxybenzamide, full agonist, > 200-fold binding selectivity over D₄, D₂, 5-HT_1A, and α1-receptors * (-)-7--5,6,7,8-tetrahydronaphthalen-2-ol * 5-OH-DPAT * 7-OH-DPAT *

Pergolide Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced do ...

* 8-OH-PBZI (cis-8-Hydroxy-3-(n-propyl)-1,2,3a,4,5,9b-hexahydro-1H-benz ndole) * Apomorphine (non-selective dopamine agonist) * Bromocriptine (non-selective dopamine agonist) * Captodiame * CJ-1639 * compound ''R,R''-16: 250x binding selectivity over D₂ *

Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

(endogenous agonist) *

ES609 ECMAScript (; ES) is a JavaScript standard intended to ensure the interoperability of web pages across different browsers. It is standardized by Ecma International in the documenECMA-262 ECMAScript is commonly used for client-side scripting ...

* FAUC 54 * FAUC 73 *

PD-128,907 PD-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 ...

PF-219,061 PF-219,061 is a drug that was under development by Pfizer which acts as a potent and highly selective agonist for the dopamine D3 receptor. It was under development as a potential medication for the treatment of female sexual dysfunction. It ...

(extremely selective) *

PF-592,379 PF-592,379 is a drug developed by Pfizer which acts as a potent, selective and orally active agonist for the dopamine D3 receptor, which is under development as a potential medication for the treatment of female sexual dysfunction and male ere ...

Piribedil Piribedil (trade names Pronoran, Trivastal Retard, Trastal, Trivastan, Clarium and others) is an antiparkinsonian agent and piperazine derivative which acts as a D2 and D3 receptor agonist. It also has α2-adrenergic antagonist properties. ...

(non-selective dopamine agonist) * Pramipexole (non-selective dopamine agonist) *

Quinelorane Quinelorane is a drug which acts as a dopamine agonist for the D2 and D3 receptor. See also * Quinpirole References Dopamine agonists Aminopyrimidines {{nervous-system-drug-stub ...

(also D2 agonist) *

Quinpirole Quinpirole is a psychoactive drug and research chemical which acts as a selective D2 and D3 receptor agonist. It is used in scientific research. Quinpirole has been shown to increase locomotion and sniffing behavior in mice treated with it. At ...

(also D2 agonist) *

Ropinirole Ropinirole, sold under the brand name Requip among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In PD the dose needs to be adjusted to the effect and treatment should not be suddenly stopped. ...

(non-selective dopamine agonist) * Rotigotine (non-selective dopamine agonist)

Partial agonists

Aripiprazole Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...

(non-selective) * BP-897 *

Brexpiprazole Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic. It is a dopamine D2 receptor partial agonist and has been described as a "serotonin–dopamine activity modulator" (SDAM). The drug was approved by the ...

(non-selective) *

Buspirone Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to fo ...

(non-selective) * Cariprazine * CJB 090 * CJ-1037 (extremely selective) * FAUC 460 (highly selective) * FAUC 346 (highly selective) * Pardoprunox (non-selective) * Roxindole (possibly a partial agonist at the D3 autoreceptors, non-selective) * OS-3-106 * UH-232 * WW-III-55

Antagonists

* Most

Antipsychotics Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...

Amisulpride Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold un ...

(non-selective) *

Cyproheptadine Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine, first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties. It was patented in 1959 an ...

(non-selective) * PG 01037 *

Domperidone Domperidone, sold under the brand name Motilium among others, is a dopamine antagonist medication which is used to treat nausea and vomiting and certain gastrointestinal problems like gastroparesis (delayed gastric emptying). It raises the l ...

(peripheral D₂ and D₃ antagonist) * FAUC 365, silent

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

, subtype selective * GR-103,691 * GSK598809 (highly selective) *

Haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

(non-selective, blocks all dopamine receptor subtypes, though D3 with the strongest affinity) * N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides * Nafadotride * NGB-2904 * PNU-99,194 (moderately selective over D2) * Raclopride (also D2 antagonist) * S-14,297 (selective) * S33084 * SB-277011-A, 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 * SR 21502 (highly selective) *

Sulpiride Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic (although some texts have referred to it as a typical antipsychotic) medication of the benzamide class which is used mainly in the treatment of psychosis ...

(also D2 antagonist) * U99194 * YQA14 (high affinity and selectivity) *

Risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions ...

Interactions

Dopamine receptor D₃ has been shown to

interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...

with CLIC6 and

EPB41L1 Band 4.1-like protein 1 is a protein that in humans is encoded by the ''EPB41L1'' gene. Function Erythrocyte membrane protein band 4.1 (EPB41) is a multifunctional protein that mediates interactions between the erythrocyte cytoskeleton and t ...

. DRD3 Ser9Gly polymorphism(rs6280), which is a single nucleotide polymorphism (SNP) with variant base C/T is linked to variation in PD such as depression severity, impulse control disorders, behavioral addiction and aberrant decision-making.

References

External links

* * {{G protein-coupled receptors Dopamine receptors Biology of attention deficit hyperactivity disorder