Dopamine receptor D1
|Dopamine receptor D1|
|Symbols||; DADR; DRD1A|
|External IDs||IUPHAR: ChEMBL: GeneCards:|
|RNA expression pattern|
This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G protein-coupled receptor stimulates adenylate cyclase and indirectly activates cyclic AMP-dependent protein kinases. D1 receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D2-mediated events. Alternate transcription initiation sites result in two transcript variants of this gene.
The DRD1 gene expresses primarily in the caudate putamen in humans, and in the caudate putamen, the nucleus accumbens and the olfactory tubercle in mouse. Gene expression patterns from the Allen Brain Atlases in mouse and human can be found here.
There are a number of ligands selective for the D1 receptors. To date, most of the known ligands are based on dihydrexidine or the prototypical benzazepine partial agonist SKF-38393 (one derivative being the prototypical antagonist SCH-23390). None of the known ligands is selective for the D1 vs. the D5 receptor, but the benzazepines generally are more selective for the D1 and D5 receptors versus the D2-like family. Some of the benzazepines have high intrinsic activity whereas others do not.
- A-86929 - full agonist with 14-fold selectivity for D1-like receptors over D2
- 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. It also showed profound antiparkinson effects in MPTP-treated primates, but caused profound hypotension in one early clinical trial in Parkinson's disease. Although dihydrexidine has significant D2 properties, it is highly biased at D2 receptors and was used for the first demonstration of functional selectivity with dopamine receptors.
- Dinapsoline - full agonist with 5-fold selectivity for D1-like receptors over D2
- Dinoxyline - full agonist with approximately equal affinity for D1-like and D2 receptors
- Doxanthrine - full agonist with 168-fold selectivity for D1-like receptors over D2
- SKF-81297 - 200-fold selectivity for D1 over any other receptor
- SKF-82958 - 57-fold selectivity for D1 over D2
- SKF-38393 - very high selectivity for D1 with negligible affinity for any other receptor
- Fenoldopam - highly selective peripheral D1 receptor partial agonist used clinically as an antihypertensive
- 6-Br-APB - 90-fold selectivity for D1 over D2
- 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.
- 7,8-Dihydroxy-5-phenyl-octahydrobenzo[h]isoquinoline: extremely potent, high-affinity full agonist
- 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
- SCH-23,390 - 100-fold selectivity for D1 over D5
- SKF-83,959 - 7-fold selectivity for D1 over D5 with negligible affinity for other receptors; acts as an antagonist at D1 but as an agonist at D5
- Ecopipam (SCH-39,166) - a selective D1/D5 antagonist that was being developed as an anti-obesity medication but was discontinued
Dopamine receptor D1 has been shown to interact with:
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- Li M, Bermak JC, Wang ZW, Zhou QY (2000). "Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280).". Mol. Pharmacol. 57 (3): 446–52.
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- Receptors, Dopamine D1 at the US National Library of Medicine Medical Subject Headings (MeSH)