Quetiapine

Quetiapine is a dibenzothiazepine derivative. Quetiapine has a stronger antagonistic effect on 5-HT2A receptors than on dopamine D2 receptors. Under normal conditions, activation of 5-HT2A receptors stimulates phospholipase Cβ through Gq/11 protein coupling, increases IP3/DAG, raises cytosolic calcium, and activates protein kinase C, thereby increasing the excitability of cortical pyramidal neurons. When quetiapine inhibits 5-HT2A receptors, this excitability is reduced. When dopamine D2 receptors are activated, they inhibit adenylyl cyclase through Gi/o protein coupling, decrease cAMP, and reduce neuronal firing. However, quetiapine antagonizes dopamine D2 receptors, which suppresses excessive dopamine signaling in the mesolimbic pathway and reduces the generation of psychotic symptoms.