Dopamine receptor D5 (DRD5) (DRD5)

The Dopamine receptor D5 (DRD5), historically referred to as the D1B receptor, is a G protein-coupled receptor that belongs to the D1-like receptor family [1, 2]. It is primarily expressed in the brain, specifically within the hippocampus, thalamus, and hypothalamus, where it exhibits a significantly higher affinity for dopamine than the D1 receptor [1, 3]. DRD5 functions by coupling to Gs proteins to stimulate adenylyl cyclase, thereby increasing intracellular cAMP levels and modulating neuronal excitability and synaptic plasticity [2, 4]. This receptor is integral to cognitive processes such as memory and executive function, and it also plays a role in the peripheral regulation of blood pressure and sodium excretion in the kidneys [1, 4]. Clinical interest in DRD5 stems from its association with various conditions, including attention deficit hyperactivity disorder (ADHD), schizophrenia, and Parkinson's disease [3, 5]. Pharmacologically, it is often targeted by non-selective D1-like agonists and antagonists, making specific therapeutic intervention challenging due to its high structural similarity to the D1 receptor [2]. Despite these challenges, DRD5 remains a target of interest for its unique distribution and high constitutive activity compared to other dopamine receptors [1, 2]. Sources: [1] UniProt (P21918); [2] IUPHAR/BPS Guide to Pharmacology; [3] NCBI Gene (1816); [4] StatPearls (Dopamine Receptors); [5] PubMed (PMID: 18337424).

Other names

D1B dopamine receptorDopamine D5 receptorDRD1BD1-beta dopamine receptorCentral dopamine receptor D1BD1L2

Agonism of the DRD5 receptor stimulates Gs proteins, leading to the activation of adenylyl cyclase and increased intracellular cAMP levels, while antagonism blocks endogenous dopamine binding to inhibit these signaling pathways [1, 2, 4].