Antipsychotic medications are the primary pharmacologic treatment for schizophrenia and were initially discovered fortuitously in the early 1950s. Chlorpromazine was the prototype of this class of medications, retroactively noted as first-generation antipsychotics, which are primarily characterized by their high-affinity antagonism at the dopamine D2 receptor. The rediscovery of clozapine in 1989 heralded the initial era of second-generation antipsychotics, which extended through 2002. In general, second-generation antipsychotics have lower D2 affinity, along with high serotonin 5-HT2A antagonist affinity. Subsequently, several new second-generation drugs were introduced: asenapine and iloperidone in 2009, lurasidone hydrochloride in 2010, and cariprazine and brexpiprazole in 2015.
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Kantrowitz JT. The Potential Role of Lumateperone—Something Borrowed? Something New? JAMA Psychiatry. 2020;77(4):343–344. doi:10.1001/jamapsychiatry.2019.4265
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