5-hydroxytryptamine receptor 2A (5-HT2A) and Dopamine D2 receptor (D2) (5-HT2A/D2)

The combined 5-HT2A/D2 receptor network is a pharmacological target profile defined by the concurrent modulation of the 5-hydroxytryptamine receptor 2A and the dopamine D2 receptor [UniProt P28223, P14416]. This dual-target mechanism is the hallmark of atypical antipsychotics, which are designed to treat schizophrenia and other psychotic disorders with a lower risk of motor side effects compared to traditional neuroleptics [StatPearls NBK459150]. Antagonism of D2 receptors in the mesolimbic pathway reduces positive symptoms such as hallucinations and delusions [PMID: 2569224]. Concomitant 5-HT2A antagonism is thought to increase dopamine release in the nigrostriatal and mesocortical pathways, thereby mitigating extrapyramidal symptoms and potentially improving negative symptoms and cognitive function [PMID: 1970227]. The relative affinity for these two receptors, often referred to as the Meltzer ratio, is a critical determinant of the drug's clinical profile and side effect burden [PMID: 2569224]. This network remains a central focus in neuropsychiatric drug development for achieving balanced efficacy and safety [Stahl's Essential Psychopharmacology].

Other names

Serotonin-Dopamine Antagonist profileSDA5-HT2A/D2 receptor systemAtypical antipsychotic target profileHTR2A/DRD2

Simultaneous antagonism or partial agonism of the serotonin 5-HT2A receptor and the dopamine D2 receptor to modulate dopaminergic pathways [PMID: 2569224].