Dopamine D1 receptor family (D1-like receptors) (D1-like receptors)

The Dopamine D1 receptor family, also known as the D1-like receptors, comprises the D1 (DRD1) and D5 (DRD5) receptor subtypes, which are G protein-coupled receptors (GPCRs) primarily coupled to the stimulatory Gs/Golf proteins (1.3.2). Upon activation by dopamine, these receptors stimulate adenylyl cyclase, leading to increased intracellular cyclic AMP (cAMP) levels and the activation of protein kinase A (PKA) signaling pathways (1.3.1). They are widely expressed in the central nervous system, particularly in the striatum, prefrontal cortex, and hippocampus, where they modulate critical functions such as motor control, working memory, attention, and reward processing (1.3.5). Dysregulation of D1-like receptor signaling is associated with various neuropsychiatric and neurodegenerative disorders, including Parkinson's disease, schizophrenia, and ADHD (1.3.2, 1.4.4). Pharmacological agents targeting this family include agonists like fenoldopam and dihydrexidine, which are investigated for their potential to improve motor and cognitive symptoms, as well as antagonists like ecopipam (1.4.3). Therapeutic development remains focused on achieving selectivity and overcoming challenges such as hypotension and dyskinesia associated with receptor activation (1.4.1, 1.4.3).

Other names

D1-like dopamine receptors (1.3.2)D1-like receptors (1.3.2)D1/D5 receptor family (1.3.1)D1-type dopamine receptors (1.4.1)

Agonists bind to the D1-like receptors, promoting their coupling to stimulatory G proteins (Gs or Golf), which activates adenylyl cyclase to increase intracellular cAMP levels and activate protein kinase A (PKA) and downstream signaling cascades like ERK1/2 (1.3.1, 1.3.2). Some members, particularly D5, can also couple to Gq proteins to activate phospholipase C and increase intracellular calcium (1.2.3).