Dopamine receptor D2 and Dopamine receptor D3 (D2R and D3R)

Dopamine receptor D2 and dopamine receptor D3 are closely related members of the dopamine receptor subfamily of G protein-coupled receptors, predominantly coupled to Gi/o proteins. Both play essential roles in modulating neurotransmission within the central nervous system. D2 is widely expressed in the striatum and other brain regions and serves as the primary target for antipsychotic drugs, mediating effects on motor function, reward, motivation, and neuroendocrine signaling. It exists in long (D2L) and short (D2S) isoforms with distinct pre- and postsynaptic localization and functions. D3 receptor is more restricted in distribution (notably in limbic areas), involved in cognition, emotion, and motivation, and also represents a therapeutic target for both neuropsychiatric and neurodegenerative disorders. Both receptors are important drug targets, and their modulation underpins the mechanism and side effect profiles of key therapies in psychiatry and neurology. Structural studies show that D2 and D3 share the characteristic seven transmembrane domain architecture of GPCRs, with distinct ligand binding pockets that support the development of selective ligands and structure-based drug design.

Other names

D2R (for Dopamine receptor D2)D3R (for Dopamine receptor D3)DRD2 (gene symbol for D2)DRD3 (gene symbol for D3)

Antagonism (inhibition) of D2 and D3 receptors, used by most antipsychotics to reduce dopaminergic neurotransmission (especially in the mesolimbic pathway). Partial agonism of D2 (e.g., aripiprazole), resulting in stabilization of dopaminergic signaling. Agonism of D2/D3 receptors to stimulate dopaminergic pathways in Parkinson’s disease (e.g., pramipexole, ropinirole). Receptor occupancy modulates downstream cAMP levels and G-protein-dependent signaling, mostly via Gi/o protein inhibition of adenylyl cyclase.