Dopamine receptor D1

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Lua error in Module:Infobox_gene at line 33: attempt to index field 'wikibase' (a nil value). Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.[1][2][3]

Function

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.[4] Alternative transcription initiation sites result in two transcript variants of this gene.[5]

Production

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.

Ligands

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).[6] D1 receptor has a high degree of structural homologine to another dopamine receptor, D5, and they both bind similar drugs.[7] 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.[6] Some of the benzazepines have high intrinsic activity whereas others do not.

Agonists

Chemical structures of selective D1 receptor agonists.[8][9]
  • Dihydrexidine derivatives
    • A-86929 - full agonist with 14-fold selectivity for D1-like receptors over D2[6][9][10]
    • 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.[11][12] It also showed profound antiparkinson effects in MPTP-treated primates,[13] but caused profound hypotension in one early clinical trial in Parkinson's disease.[6] Although dihydrexidine has significant D2 properties, it is highly biased at D2 receptors and was used for the first demonstration of functional selectivity[14] with dopamine receptors.[15][16]
    • Dinapsoline - full agonist with 5-fold selectivity for D1-like receptors over D2[6]
    • Dinoxyline - full agonist with approximately equal affinity for D1-like and D2 receptors[6]
    • Doxanthrine - full agonist with 168-fold selectivity for D1-like receptors over D2[6]
  • Benzazepine derivatives
  • 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[17]
    • 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

Antagonists

  • Benzazepine derivatives
    • SCH-23,390 - 100-fold selectivity for D1 over D5[6]
    • SKF-83,959 - 7-fold selectivity for D1 over D5 with negligible affinity for other receptors;[6] 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[6]

Protein–protein interactions

Dopamine receptor D1 has been shown to interact with:

Receptor oligomers

The D1 receptor forms heteromers with the following receptors: dopamine D2, D3,[20] histamine H3,[21] μ opioid.[22]

See also

References

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  9. ↑ 9.0 9.1 Lua error in package.lua at line 80: module 'strict' not found.
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  18. ↑ 18.0 18.1 Lua error in package.lua at line 80: module 'strict' not found.
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External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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