Dopamine D2 receptor long isoform (D2L)

Dopamine D2 receptor long isoform (D2L) is one of two major splice variants of the dopamine D2 receptor, arising from alternative splicing that inserts 29 amino acids into the third intracellular loop of the protein. D2L is a heptahelical G protein-coupled receptor (GPCR) predominantly localized postsynaptically in the brain, especially in the striatum and nucleus accumbens, where it mediates key aspects of dopaminergic neurotransmission, including the regulation of motor activity and the modulation of hormone release from the pituitary gland[1][3][4][7]. D2L, together with D2S, constitutes the primary molecular target for typical and atypical antipsychotic drugs, as well as for some drugs used in Parkinson's disease and other neuropsychiatric disorders[2][5][6][8]. The long isoform is pharmacologically similar to the short isoform but displays distinct functional specialization, with D2L chiefly mediating postsynaptic responses. Therapeutic agents targeting D2L may cause side effects such as extrapyramidal symptoms and elevated prolactin, presenting challenges for drug development[1][2][7].

Other names

D2-long isoformD2LDRD2L

Antagonism (typical antipsychotics block D2L), Partial agonism (third generation antipsychotics modulate activity, acting as partial agonists), Modulation of postsynaptic dopamine signaling