Dopamine receptor D1

Dopamine receptor D1, also known as DRD1, is a is_associated_with::protein that in humans is encoded by the DRD1 is_associated_with::gene.

Function
This gene encodes the D1 subtype of the is_associated_with::dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This is_associated_with::G protein-coupled receptor stimulates is_associated_with::adenylate cyclase and indirectly activates is_associated_with::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.

Production
The DRD1 gene expresses primarily in the is_associated_with::caudate putamen in humans, and in the is_associated_with::caudate putamen, the is_associated_with::nucleus accumbens and the is_associated_with::olfactory tubercle in mouse. Gene expression patterns from the is_associated_with::Allen Brain Atlases in mouse and human can be found here.

Ligands
There are a number of ligands selective for the D1 receptors. To date, most of the known ligands are based on is_associated_with::dihydrexidine or the prototypical benzazepine partial agonist SKF-38393 (one derivative being the prototypical antagonist SCH-23390). D1 receptor has a high degree of structural homologine to another dopamine receptor, D5, and they both bind similar drugs. As a result, 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.

Agonists

 * Dihydrexidine derivatives
 * is_associated_with::A-86929 - full agonist with 14-fold selectivity for D1-like receptors over D2
 * is_associated_with::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 is_associated_with::Parkinson's disease. Although is_associated_with::dihydrexidine has significant D2 properties, it is highly biased at D2 receptors and was used for the first demonstration of is_associated_with::functional selectivity with dopamine receptors.
 * is_associated_with::Dinapsoline - full agonist with 5-fold selectivity for D1-like receptors over D2
 * is_associated_with::Dinoxyline - full agonist with approximately equal affinity for D1-like and D2 receptors
 * is_associated_with::Doxanthrine - full agonist with 168-fold selectivity for D1-like receptors over D2


 * Benzazepine derivatives
 * is_associated_with::SKF-81297 - 200-fold selectivity for D1 over any other receptor
 * is_associated_with::SKF-82958 - 57-fold selectivity for D1 over D2
 * is_associated_with::SKF-38393 - very high selectivity for D1 with negligible affinity for any other receptor
 * is_associated_with::Fenoldopam - highly selective peripheral D1 receptor partial agonist used clinically as an is_associated_with::antihypertensive
 * is_associated_with::6-Br-APB - 90-fold selectivity for D1 over D2
 * Others
 * is_associated_with::Stepholidine - alkaloid with D1 agonist and D2 antagonist properties, showing antipsychotic effects
 * is_associated_with::A-68930
 * is_associated_with::A-77636
 * is_associated_with::CY-208,243 - high intrinsic activity partial agonist with moderate selectivity for D1-like over D2-like receptors, member of is_associated_with::ergoline ligand family like is_associated_with::pergolide and is_associated_with::bromocriptine.
 * SKF-89145
 * SKF-89626
 * 7,8-Dihydroxy-5-phenyl-octahydrobenzo[h]isoquinoline: extremely potent, high-affinity full agonist
 * is_associated_with::Cabergoline - weak D1 agonism, highly selective for D2, and various serotonin receptors
 * is_associated_with::Pergolide - (similar to cabergoline) weak D1 agonism, highly selective for D2, and various serotonin receptors

Antagonists

 * Benzazepine derivatives
 * is_associated_with::SCH-23,390 - 100-fold selectivity for D1 over D5
 * is_associated_with::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
 * is_associated_with::Ecopipam (SCH-39,166) - a selective D1/D5 antagonist that was being developed as an is_associated_with::anti-obesity medication but was discontinued

Protein-protein interactions
Dopamine receptor D1 has been shown to interact with:
 * is_associated_with::COPG2,
 * is_associated_with::COPG, and
 * is_associated_with::DNAJC14.

Receptor oligomers
The D1 receptor forms heteromers with the following receptors: dopamine D2, D3, histamine H3, μ opioid.