Dopamine receptor D1
Encyclopedia
Dopamine receptor D1, also known as DRD1, is a protein
that in humans is encoded by the DRD1 gene
.
. 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.
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.
with COPG
, DNAJC14
and COPG2
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the DRD1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
This gene encodes the D1 subtype of the dopamine receptorDopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
. 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
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
-mediated events. Alternate transcription initiation sites result in two transcript variants of this gene.
Ligands
There are a number of ligands selective for the D1 receptors. They comprise almost exclusively of compounds derived from dihydrexidineDihydrexidine
Dihydrexidine is a moderately selective full agonist at the dopamine D1 and D5 receptors. It has approximately 10-fold selectivity for D1 and D5 over the D2 receptor. Although dihydrexidine has some affinity for the D2 receptor, it has functionally selective D2 signaling, thereby explaining...
and from the prototypical benzazepine
Benzazepines
Benzazepines are heterocyclic compounds consisting of a benzene ring fused to an azepine ring. Examples include fenoldopam....
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.
Agonists
- Dihydrexidine derivatives
- A-86,929 - full agonist with 14-fold selectivity for D1-like receptors over D2
- DihydrexidineDihydrexidineDihydrexidine is a moderately selective full agonist at the dopamine D1 and D5 receptors. It has approximately 10-fold selectivity for D1 and D5 over the D2 receptor. Although dihydrexidine has some affinity for the D2 receptor, it has functionally selective D2 signaling, thereby explaining...
- full agonist with 10-fold selectivity for D1-like receptors over D2 that was being investigated for the treatment of Parkinson's diseaseParkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system...
but was discontinued due to intolerable side effects - DinapsolineDinapsolineDinapsoline is a drug developed for the treatment of Parkinson's disease, that acts as a selective full agonist at the dopamine D1 receptor....
- full agonist with 5-fold selectivity for D1-like receptors over D2 - DinoxylineDinoxylineDinoxyline is a synthetic compound developed for scientific research, which acts as a potent full agonist at all five dopamine receptor subtypes....
- full agonist with approximately equal affinity for D1-like and D2 receptors - DoxanthrineDoxanthrineDoxanthrine is a synthetic compound which is a potent and selective full agonist for the dopamine D1 receptor....
- 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
- FenoldopamFenoldopamFenoldopam is a drug and synthetic benzazepine derivative which acts as a peripheral selective D1 receptor weak partial agonist/antagonist and is used as an antihypertensive. It was approved by the Food and Drug Administration in September 1997...
- highly selective peripheral D1 receptor partial agonist used clinically as an antihypertensiveAntihypertensiveThe antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from... - 6-Br-APB6-Br-APB6-Br-APB is a synthetic compound that acts as a selective D1 agonist, with the -enantiomer being a potent full agonist, while the enantiomer retains its D1 selectivity but is a weak partial agonist...
- 90-fold selectivity for D1 over D2
- Others
- A-68,930
- A-77,636
- CY-208,243CY-208,243CY-208,243 is a drug which acts as a dopamine agonist selective for the D1 subtype. Unlike most D1-selective agonists, it shows efficacy in animal models of Parkinson's disease....
- partial agonist with moderate selectivity for D1-like over D2-like receptors, structurally most closely related to ergolineErgolineErgoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs . Ergoline derivatives are used clinically for the purpose of vasoconstriction and in the treatment of migraines and Parkinson's disease...
-based dopamine agonists like pergolidePergolidePergolide is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease....
. - SKF-89,145
- SKF-89,626
- 7,8-Dihydroxy-5-phenyl-octahydrobenzo[h]isoquinoline: extremely potent, high-affinity full agonist
-
- CabergolineCabergolineCabergoline , an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph cells...
- weak D1 agonism, highly selective for D2, and various serotonin receptors - PergolidePergolidePergolide is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease....
- (similar to cabergoline) weak D1 agonism, highly selective for D2, and various serotonin receptors
- Cabergoline
Antagonists
- 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
- EcopipamEcopipamEcopipam is a synthetic benzazepine derivative drug that acts as a selective dopamine D1/D5 receptor antagonist, with little affinity for either dopamine D2-like or 5-HT2 receptors...
(SCH-39,166) - a selective D1/D5 antagonist that was being developed as an anti-obesity medication but was discontinued
Interactions
Dopamine receptor D1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with COPG
COPG
Coatomer subunit gamma is a protein that in humans is encoded by the COPG gene.-Interactions:COPG has been shown to interact with Dopamine receptor D1, COPZ1 and COPB1.-Further reading:...
, DNAJC14
DNAJC14
DnaJ homolog subfamily C member 14 is a protein that in humans is encoded by the DNAJC14 gene.-Interactions:DNAJC14 has been shown to interact with Dopamine receptor D1.-Further reading:...
and COPG2
COPG2
Coatomer subunit gamma-2 is a protein that in humans is encoded by the COPG2 gene.-Interactions:COPG2 has been shown to interact with Dopamine receptor D1 and COPB1.-Further reading:...
.