A Comprehensive Monograph on Iloperidone (Fanapt®): Pharmacology, Clinical Efficacy, and Therapeutic Niche

Introduction and Drug Profile

Overview and Classification

Iloperidone is a second-generation, or "atypical," antipsychotic agent belonging to the piperidinyl-benzisoxazole chemical class.[1] As a synthetic organic small molecule, its therapeutic effects are primarily derived from its activity as a potent antagonist at multiple neurotransmitter receptor sites, most notably serotonergic and dopaminergic systems.[1] Structurally related to the atypical antipsychotic risperidone, iloperidone was developed with the objective of providing robust antipsychotic efficacy while minimizing the incidence of extrapyramidal symptoms (EPS), a class of motor side effects commonly associated with older, first-generation antipsychotics and some second-generation agents.[2]

Iloperidone is classified pharmacologically as a multi-receptor antagonist, with a binding profile that distinguishes it from other agents in its class. Its primary mechanism is understood to involve a combination of dopamine type 2 (D2​) and serotonin type 2A (5−HT2A​) receptor blockade.[1] This dual action is a hallmark of atypical antipsychotics and is believed to be central to their broader spectrum of efficacy against both positive and negative symptoms of schizophrenia, as well as their improved motor tolerability profile.

Key Therapeutic Indications and Clinical Context

Iloperidone is approved by the United States Food and Drug Administration (FDA) for two primary indications in adults: the treatment of schizophrenia and the acute treatment of manic or mixed episodes associated with bipolar I disorder.[1] The initial approval for schizophrenia was granted on May 6, 2009, with the indication for bipolar I disorder following in April 2024, based on new clinical trial data.[6]