Dopamine receptor D2 long isoform and Dopamine receptor D3 (D2L, D3)

Dopamine receptor D2 long isoform (D2L) and dopamine receptor D3 (D3) are members of the D2-like family of G protein-coupled receptors (GPCRs). Both are integral membrane proteins that modulate neurophysiological functions by inhibiting adenylyl cyclase and reducing cAMP levels via Gi/Go coupling. D2L is primarily expressed postsynaptically in various brain regions and is a major target for neuroleptics (antipsychotics). D3 receptor is highly expressed in limbic regions such as the nucleus accumbens, with roles in cognition, motivation, emotion, and reward. Both participate in dopaminergic signaling relevant to psychiatric, neurological, and addictive disorders. Drugs targeting these receptors include antipsychotics, dopamine agonists for Parkinson’s, and experimental compounds for substance abuse. Their pharmacology is central to treatment efficacy and safety, including risk of movement disorders (EPS) and neuroendocrine effects. The two receptors share a high degree of structural homology but display distinct expression profiles and functional roles within the central nervous system.

Other names

Dopamine D2L receptorDRD2LD2 long isoformDopamine D3 receptorDRD3

Antagonists: Block dopamine binding and receptor activation, reducing dopamine signaling—major mechanism for antipsychotic efficacy. Agonists: Stimulate these receptors, beneficial in Parkinson’s disease for motor symptoms. Partial agonists: Modulate dopamine signaling in a context-dependent manner. Modulation of adenylate cyclase inhibition and synaptic neurotransmission.