Clinical meaning
Extrapyramidal symptoms (EPS) are a group of movement disorders caused by dopamine receptor blockade in the nigrostriatal pathway of the basal ganglia. The basal ganglia (caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra) modulate voluntary motor activity through a delicate balance between dopaminergic (D2) and cholinergic (muscarinic) neurotransmission. Dopamine normally INHIBITS the indirect pathway (reducing unwanted movement) and FACILITATES the direct pathway (enabling intended movement). When D2 receptors in the striatum are blocked by antipsychotic medications, this balance shifts toward cholinergic dominance, producing the characteristic movement abnormalities of EPS. The degree of D2 receptor occupancy correlates directly with EPS risk: >80% occupancy produces clinically significant EPS; 60-80% provides antipsychotic efficacy with lower EPS risk; <60% may be subtherapeutic. First-generation antipsychotics (FGAs/typicals: haloperidol, chlorpromazine, fluphenazine) are high-potency D2 blockers with high EPS risk. Second-generation antipsychotics (SGAs/atypicals: risperidone, olanzapine, quetiapine) have lower D2 affinity plus 5-HT2A antagonism, which increases dopamine release in the nigrostriatal pathway, partially compensating for D2 blockade and reducing EPS risk. However, SGAs are NOT free of EPS risk, especially at higher doses. EPS are classified by onset:...