Dopamine Receptors

Dopamine is the major catecholamine neurotransmitter present in the mammalian brain where it is responsible for a variety of functions, including locomotion, neuroendocrine secretion, cognition and emotion. Dopamine also plays a role in the periphery where it regulates a range of other processes, including catecholamine release, hormone secretion, and gastrointestinal motility.

Targets
Literature
Receptor Data

The application of molecular cloning techniques to the study of dopamine receptors has expanded the classical dopamine D1/D2 classification scheme to include five dopamine receptor subtypes. These may be divided into D1-like (D1 and D5) and D2-like (D2, D3 and D4 receptors) based on their predicted transmembrane topologies, and functional and pharmacological properties. Dysregulation of dopamine transmission causes a variety of conditions such as Parkinson's disease, Tourette's syndrome, schizophrenia and hyperprolactemia.

Literature for Dopamine Receptors

GPCR

GPCR Product Listing

A collection of over 450 products for G protein-coupled receptors, the listing includes research tools for the study of:

  • Rhodopsin-like Receptors
  • Secretin-like Receptors
  • Glutamate Receptors
  • Frizzled Receptors
  • GPCR Signaling
Neurodegeneration

Neurodegeneration Product Guide

A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

  • Alzheimer's disease
  • Parkinson's disease
  • Huntington's disease
Dopamine Receptors

Dopamine Receptors Scientific Review

Written by Phillip Strange and revised by Kim Neve in 2013, this review summarizes the history of the dopamine receptors and provides an overview of individual receptor subtype properties, their distribution and identifies ligands which act at each receptor subtype. Compounds available from Tocris are listed.

Addiction

Addiction Poster

The key feature of drug addiction is the inability to stop using a drug despite clear evidence of harm. This poster describes the brain circuits associated with addiction, and provides an overview of the main classes of addictive drugs and the neurotransmitter systems that they target.

Depression

Depression Poster

Major depressive disorder is characterized by depressed mood and a loss of interest and/or pleasure. Updated in 2015 this poster highlights presynaptic and postsynaptic targets for the potential treatment of major depressive disorder, as well as outlining the pharmacology of currently approved antidepressant drugs.

Parkinson's

Parkinson's Poster

Parkinson's disease (PD) causes chronic disability and is the second most common neurodegenerative condition. This poster outlines the neurobiology of the disease, as well as highlighting current therapeutic treatments for symptomatic PD, and emerging therapeutic strategies to delay PD onset and progression.

Schizophrenia

Schizophrenia Poster

Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.

Dopamine Receptor Data

Receptor Subtype D1-like Receptors D2-like Receptors
D1 D5 D2 D3 D4
G protein Gs Gs Gi/o Gi/o Gi/o
Transduction Mechanism ↑ AC, ↑ PLC, ↑ L-type Ca2+ channels ↑ AC ↓ AC, ↑ [Ca2+]i, K+ conductance, ↓ Ca2+ conductance ↓ AC, activation of MAP kinase ↓ AC, ↓ Ca2+ conductance
Localization Caudate, putamen, nucleus accumbens, olfactory tubercle Hippocampus, hypothalamus Caudate, putamen, nucleus accumbens, olfactory tubercle Nucleus accumbens, olfactory tubercle, islands of Calleja Frontal cortex, midbrain, amygdala, cardiovascular system
Likely Physiological Roles Locomotion, reward, reinforcement, learning and memory, renin secretion Learning and memory Locomotion, reward, reinforcement, learning and memory Locomotion, possible role in cognition and emotion Mostly unknown - possible role in cognition and emotion, hypertension

Key Compounds Ki Values (nM)
D1-like Agonists SKF 38393 (0922)
SKF 83822 (2075)
1
3.2
~ 0.5
3.1
~ 150
186
~ 5000
66
~ 1000
335
D1-like Antagonists SCH 23390 (0925) ~ 0.2 0.3 ~ 1100 ~ 800 ~ 3000
D2-like Agonists Bromocriptine (0427)
7-HydroxyDPAT (0706)
Cabergoline (2664)
~ 440
~ 5000
-
~ 450
-
165
~ 8
10
0.7
~ 5
~ 1
1.5
~ 290
650
9.0
D2-like Antagonists Clozapine (0444)
Haloperidol (0931)
Nemonapride (1746)
NGB 2904 (2635)
Raclopride (1810)
Remoxipride (0916)
Spiperone (0995)
(S)-(-)-Sulpride (0895)
~ 170
~ 80
-
> 10000
18000
-
~ 350
~ 45000
~ 330
~ 100
-
217
-
-
~ 3500
77000
~ 230
1.2
0.06
1.4
1.8
~ 300
0.06
~ 15
~ 170
~ 7
0.3
> 5000
3.5
~ 1600
0.6
~ 13
21
2.3
0.15
> 10000
2400
~ 2800
0.08
1000

All Ki values for agonists were determined at the high-affinity state for all receptors, except for D3 receptors.

References

Seeman and Van Tol (1994) Dopamine receptor pharmacology. TiPS 15 264. Missale et al (1998) Dopamine receptors: from structure to function. Physiol.Rev. 78 189. O'Sullivan et al (2004) SK&F 83822 distinguishes adenylyl cyclase from phospholipase C-coupled D1-like receptors: behavioural topography. Eur.J.Pharmacol. 486 273. Kvernmo et al (2006) A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin.Ther. 28 1065. Yuan et al (1998) NGB 2904 and NGB 2849: two highly selective dopamine D3 receptor antagonists. Bioorg.Med.Chem.Lett. 8 2715.