Figure 4.

Pathophysiological mechanisms underlying the induction of extrapyramidal side effects (EPS) with antipsychotic treatments. Antipsychotic drugs commonly exert dopamine D₂ blocking actions in the striatum, which relieves the striatal neurons (GABA-containing medium spiny neurons and acetylcholine (ACh)-containing interneurons) from negative regulation by the nigrostriatal dopaminergic neurons. Thus, overall activation of striatal medium spiny neurons by antipsychotics evokes EPS (e.g., bradykinesia, tremor, and muscle rigidity). Antipsychotic-induced EPS can be alleviated by anti-muscarinic drugs (e.g., trihexyphenidyl and biperidene), which reverses the imbalance between dopamine and ACh neuron activities in the striatum. However, due to the side effects, these agents are not recommended for the elderly patients.