Dopamine D1-like and D3 receptors (D1-like/D3R)

The Dopamine D1-like (comprising D1 and D5) and D3 receptors are critical components of the dopaminergic system, primarily expressed in the central nervous system where they modulate motor, cognitive, and emotional functions (StatPearls, 2023). D1-like receptors are typically coupled to Gs/Golf proteins, stimulating adenylyl cyclase and increasing intracellular cAMP, while the D3 receptor belongs to the D2-like family and is coupled to Gi/o proteins, which inhibit cAMP production (Beaulieu & Gainetdinov, 2011). These receptors are often co-localized in brain regions such as the nucleus accumbens and dorsal striatum, where they can form D1-D3 receptor heteromers that exhibit unique pharmacological properties and synergistic signaling (Marcellino et al., 2008). In clinical practice, D1 and D3 receptors are targeted for the treatment of Parkinson's disease to alleviate motor deficits and in schizophrenia to manage both positive and negative symptoms (NIH, 2023). Drugs like cariprazine act as D3/D2 partial agonists with high D3 affinity, while rotigotine provides non-selective agonism across D1, D2, and D3 receptors to treat movement disorders (PubChem, 2024). The interplay between these signaling pathways is also a major focus in addiction research, as D3 receptors specifically play a significant role in drug-seeking behavior and relapse (Heidbreder et al., 2005).

Other names

D1 and D3 dopamine receptorsD1-like/D3 receptor complexDRD1/DRD5 and DRD3D1-D3 receptor heteromers

Agonism, Partial agonism, Antagonism, Allosteric modulation