Dopamine D2 receptor and Dopamine D3 receptor (D2R (for dopamine D2 receptor), D3R (for dopamine D3 receptor))

Dopamine D2 receptor (D2R) and dopamine D3 receptor (D3R) are closely related members of the D2-like dopamine receptor subfamily within the G protein–coupled receptor (GPCR) superfamily. Both are seven-transmembrane receptors that couple to inhibitory Gi/o proteins, leading to inhibition of adenylyl cyclase and modulation of diverse intracellular signaling pathways[1][5][7]. D2R is the primary molecular target for most antipsychotic drugs and is widely expressed in key brain regions implicated in movement, motivation, and psychosis[3][5]. D3R, while highly homologous to D2R, shows a more restricted distribution in limbic areas and is less abundant; it is a focus of drug discovery efforts for disorders involving reward and addiction[4][6]. These receptors have important roles in modulating neurotransmission, regulating hormonal secretions, and mediating the effects of therapeutic agents and drugs of abuse. Their blockade or modulation underlies both the clinical efficacy and side effects of many psychiatric medications, especially for schizophrenia and related disorders[2][4][7]. Selective targeting of D3R, compared to D2R, is of interest for potential reduction in motor side effects and for treatment of cognitive and negative symptoms[4].

Other names

D2 receptor (D2R)DRD2 (gene/protein symbol for dopamine D2 receptor)D3 receptor (D3R)DRD3 (gene/protein symbol for dopamine D3 receptor)Dopamine receptor D2Dopamine receptor D3

Antagonism: Many antipsychotics act as antagonists or partial agonists at D2 and D3 receptors, blocking dopamine signaling linked to positive symptoms of psychosis[5][2][4]. Partial agonism: Some drugs modulate dopaminergic tone without full blockade (e.g., aripiprazole as a partial agonist)[2]. Dopamine autoreceptor regulation: Presynaptic D2 receptors regulate dopamine release; antagonists increase dopamine tone[5]. Agonist/antagonist modulation of signaling pathways (Gi/o inhibition of adenylyl cyclase, alteration of intracellular calcium)[7][5].