Dopamine D1 receptor
|Dopamine receptor D1|
|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 adenylyl cyclase and 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 here.
There are a number of ligands selective for the D1 receptors. They comprise almost exclusively of compounds derived from dihydrexidine and from the prototypical benzazepine SCH-23,390. While the benzazepines are generally highly and fully selective for the D1 receptor over all other receptors, the dihydrexidine derivatives do not distinguish between the D1 and D5 receptors and therefore cannot be said to be truly selective. The benzazepines are weak partial agonists/antagonists with low intrinsic activity, whereas the dihydrexidine derivatives function as full agonists with intrinsic activity equal to or greater than that elicited by dopamine itself.
- Dihydrexidine derivatives
- A-86,929 - 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 was being investigated for the treatment of Parkinson's disease but was discontinued due to intolerable side effects
- 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
- Benzazepine derivatives
- SKF-81,297 - 200-fold selectivity for D1 over any other receptor
- SKF-82,958 - 57-fold selectivity for D1 over D2
- SKF-38,393 - 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 - partial agonist with moderate selectivity for D1-like over D2-like receptors, structurally most closely related to ergoline-based dopamine agonists like pergolide.
- 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
- Benzazepine derivatives
- 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
- Medical Subject Headings (MeSH)