Dopamine receptor D1
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family — receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.[5][6][7][8]
Tissue distribution
D1 receptors are the most abundant kind of dopamine receptor in the central nervous system.
Lower levels occur in the basolateral amygdala, cerebral cortex, septum, thalamus, and hypothalamus.[9]
Function
D1 receptors regulate the memory, learning, and the growth of neurons, also is used in the reward system and locomotor activity, mediating some behaviors and modulating dopamine receptor D2-mediated events.[10][8]
They play a role in
They are
Production
The DRD1 gene expresses primarily in the
Ligands
There are a number of ligands selective for the D1 receptors. To date, most of the known ligands are based on
Agonists
Several D1 receptor agonists are used clinically. These include
List of D1 receptor agonists
- Dihydrexidine derivatives
- A-86929 – full agonist with 14-fold selectivity for D1-like receptors over D2[11][15][19]
- Dihydrexidine – full agonist with 10-fold selectivity for D1-like receptors over D2 that has been in Phase IIa clinical trials as a cognitive enhancer.[20][21] It also showed profound antiparkinson effects in MPTP-treated primates,[22] but caused profound hypotension in one early clinical trial in Parkinson's disease.[11] Although dihydrexidine has significant D2 properties, it is highly biased at D2 receptors and was used for the first demonstration of functional selectivity[23] with dopamine receptors.[24][25]
- Dinapsoline – full agonist with 5-fold selectivity for D1-like receptors over D2[11]
- Dinoxyline – full agonist with approximately equal affinity for D1-like and D2 receptors[11]
- Doxanthrine – full agonist with 168-fold selectivity for D1-like receptors over D2[11]
- Benzazepine derivatives
- SKF-81297 – 200-fold selectivity for D1 over any other receptor[11]
- SKF-82958 – 57-fold selectivity for D1 over D2[11]
- SKF-38393 – very high selectivity for D1 with negligible affinity for any other receptor[11]
- Clozapine – partial agonist at D1-like receptors[26]
- antihypertensive[11]
- 6-Br-APB – 90-fold selectivity for D1 over D2[11]
- Others
- Stepholidine – alkaloid with D1 agonist and D2 antagonist properties, showing antipsychotic effects
- A-68930
- A-77636
- CY-208,243 – high intrinsic activity partial agonist with moderate selectivity for D1-like over D2-like receptors, member of ergoline ligand family like pergolide and bromocriptine.
- SKF-89145
- SKF-89626
- 7,8-Dihydroxy-5-phenyl-octahydrobenzo[h]isoquinoline – extremely potent, high-affinity full agonist[27]
- Cabergoline – weak D1 agonism, highly selective for D2, and various serotonin receptors
- Pergolide – (similar to cabergoline) weak D1 agonism, highly selective for D2, and various serotonin receptors
- A photoswitchable agonist of D1-like receptors (azodopa[28]) has been described that allows reversible control of dopaminergic transmission in wildtype animals.
Antagonists
Many
List of D1 receptor antagonists
- Benzazepine derivatives
- SCH-23,390 – 100-fold selectivity for D1 over D5[11]
- Ecopipam (SCH-39,166) – a selective D1/D5 antagonist that was being developed as an anti-obesity medication but was discontinued[11] However, it has showed promise in reducing stuttering and is currently in Phase 2 Trials for this purpose[29][30]
Modulators
- DETQ –
- LY-3154207 – potent and subtype selective PAM, in phase 2 studies for Lewy body dementia.[34]
Protein–protein interactions
Dopamine receptor D1 has been shown to interact with:
Receptor oligomers
The D1 receptor forms
- D1–D2 receptor complex[37]
- D1−NMDAR receptor complex – a target to prevent neurodegeneration[41]
- D1–D3 receptor complex[37]
- D1–NMDAR receptor complex[37]
- D1–A1 receptor complex[37]
Structure
Several
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000184845 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021478 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ ISBN 9780471660538., thalamus, and hypothalamus.
Localization of the D1 receptor messenger ribonucleic acid (mRNA) expression has been mapped using Northern analysis and in situ hybridization (for a review, see [54]). Expression of D1 receptor mRNA is highest in the caudate putamen, nucleus accumbens, and olfactory tubercle. Lower levels of expression are found in the basolateral amygdala, cerebral cortex, septum pellucidum
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- ^ "First Patient Dosed in Emalex Biosciences Phase 2 Clinical Trial for Stuttering - Emalex Biosciences". 15 December 2020.
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External links
- "Dopamine Receptors: D1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2015-01-02. Retrieved 2008-12-04.
- Receptors,+Dopamine+D1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.