Dopamine receptor D2 (D2R) (D2R)

The Dopamine receptor D2 (D2R) is a G protein-coupled receptor (GPCR) that is a primary mediator of dopaminergic signaling in the central nervous system [1, 3]. It belongs to the D2-like family of receptors and is primarily coupled to Gi/o proteins, which inhibit the enzyme adenylyl cyclase and decrease intracellular cAMP levels [1, 5]. D2R is expressed in two main isoforms, D2L (long) and D2S (short), which function as post-synaptic receptors and pre-synaptic autoreceptors, respectively, to regulate dopamine release and neuronal excitability [3, 7]. This receptor plays a pivotal role in various physiological processes, including motor control, reward-seeking behavior, cognitive functions, and the regulation of prolactin secretion from the pituitary gland [3, 5]. In clinical medicine, D2R is a major therapeutic target; its antagonism is the hallmark of antipsychotic medications used to treat schizophrenia and bipolar disorder [3, 5]. Conversely, D2R agonists are essential in the treatment of Parkinson's disease and hyperprolactinemia [5, 9]. However, pharmacological modulation of D2R is often associated with significant side effects, such as extrapyramidal symptoms and metabolic changes, due to its broad influence on neural circuitry [5, 8]. Understanding the specific signaling pathways and localization of D2R continues to be a focus for developing more selective and safer neuropsychiatric therapies [6, 9].

Other names

D2 dopamine receptorDRD2D2DR

Antagonism, agonism, and partial agonism of the receptor to modulate dopaminergic signaling and downstream cAMP levels.