Target intelligence / Profile preview

Dopamine receptor (D1-like and D2-like) (DRD)

Target
DRD
Molecular classification
G protein-coupled receptor, Receptor
01

Overview

Dopamine receptors are a class of G protein-coupled receptors (GPCRs) that mediate the actions of the neurotransmitter dopamine in the central nervous system and peripheral tissues (StatPearls, 2023). They are categorized into two subfamilies based on their biochemical and pharmacological properties: the D1-like receptors (comprising D1 and D5) and the D2-like receptors (comprising D2, D3, and D4) (NIH, 2023). D1-like receptors are generally coupled to Gs proteins, stimulating adenylyl cyclase and increasing intracellular cAMP, whereas D2-like receptors are coupled to Gi/o proteins, inhibiting adenylyl cyclase and decreasing cAMP levels (UniProt, 2024). These receptors are essential for regulating motor control, motivation, reward, and executive functions (PubMed, 2022). Clinically, D2-like receptor antagonists are the cornerstone of antipsychotic therapy for schizophrenia, while D2-like agonists are used to treat Parkinson's disease and restless legs syndrome (FDA, 2023). However, targeting these receptors carries significant risks, such as extrapyramidal symptoms from D2 blockade or impulse control disorders from D3 agonism (Mayo Clinic, 2023).

Other names
Dopamine receptorsDRDsD1-like receptorsD2-like receptorsDopaminergic receptors
02

Mechanism of action

Drugs targeting these receptors act as agonists, antagonists, or partial agonists to modulate dopaminergic signaling. D1-like receptors (D1 and D5) are generally coupled to Gs proteins and stimulate adenylyl cyclase, increasing cAMP levels, while D2-like receptors (D2, D3, and D4) are coupled to Gi/o proteins and inhibit adenylyl cyclase, decreasing cAMP levels (StatPearls, 2023; NIH, 2023).

03

Biological functions

Signal transductionNeurotransmissionMotor controlReward processingCognitive functionHormone regulationRenal function regulation
04

Disease associations

SchizophreniaParkinson's diseaseAttention deficit hyperactivity disorder (ADHD)Substance use disorderBipolar disorderHyperprolactinemiaRestless legs syndrome
05

Safety considerations

Extrapyramidal symptoms (EPS)Tardive dyskinesiaHyperprolactinemiaNeuroleptic malignant syndrome (NMS)Metabolic syndrome and weight gainOrthostatic hypotensionImpulse control disorders (associated with D3 agonists)
06

Interacting drugs

Haloperidol

9 more in the full profile.

07

Biomarkers

Striatal D2 receptor occupancy (via PET/SPECT imaging)Cerebrospinal fluid Homovanillic acid (HVA) levelsSerum Prolactin levelsEye blink rate (indirect measure)

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