Iloperidone

Iloperidone is indicated for the treatment of schizophrenia and mania or mixed episodes in bipolar I disorder.^[2][3] In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, iloperidone demonstrated mild effectiveness — as effective as lurasidone, and 13 to 15% less effective than ziprasidone, chlorpromazine, and asenapine.^[4] It generally appears to work better than placebo.^[5]

Examination of the safety and tolerability of iloperidone have shown that at a 5 mg/day dose in healthy male volunteers, the drug was fairly well tolerated, although hypotension, dizziness, and somnolence were very common side effects ranging from mild to moderate in severity. A second study showed that co administration of food decreased the severity of these effects. This study also indicated that repeat administration of iloperidone could decrease the effects of hypotension.^[6]

The approved dose is 12–24 mg, not 5 mg. However, claims of better tolerance have been reported.

Iloperidone exerts its effects by acting upon and antagonizing specific neurotransmitters, particularly multiple dopamine and serotonin receptor subtypes. It is considered an 'atypical' antipsychotic because it displays serotonin receptor antagonism, similar to other atypical antipsychotics. The older typical antipsychotics are primarily dopamine antagonists.

Iloperidone has been shown to act as an antagonist at all tested receptors except for 5-HT_2A. It exhibits high (nM) affinity to serotonin 5-HT_2A (Ki value of 5.6 nM) where it acts as a inverse agonist. Antagonism occurs at all other receptors following dopamine D₂ (6.3 nM) and D₃ (7.1 nM) and α₁-adrenergic receptors (0.36 nM),^[11] moderate affinity for dopamine D₄ (25 nM), serotonin 5-HT₆ (43 nM), 5-HT₇ (22 nM), and low affinity for the serotonin 5-HT_1A (168 nM), dopamine D₁, and histamine H₁ receptors. In addition, pharmacogenomic studies identified single nucleotide polymorphisms associated with an enhanced response to iloperidone during acute treatment of schizophrenia.^[5][12]

Hoechst Marion Roussel Inc. made initial inquiries into the drug; however, in May 1996, they discontinued research, and in June 1997 gave research rights to Titan Pharmaceuticals. Titan then handed over worldwide development, manufacturing and marketing rights to Novartis in August 1998. On June 9, 2004, Titan Pharmaceuticals announced that the Phase III development rights have been acquired by Vanda Pharmaceuticals. The original launch date was scheduled for 2002. On November 27, 2007, Vanda Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) had accepted their New Drug Application for iloperidone, confirming the application is ready for FDA review and approval.^[13] On July 28, 2008, the FDA issued a not-approvable letter to Vanda Pharmaceuticals concerning the drug, stating that further trials are required before a decision can be made concerning marketed usage of iloperidone.^[14]

Iloperidone was approved by the FDA for the treatment of schizophrenia in the United States on May 6, 2009.^[15] and for treating bipolar I disorder in April 2024.^[2]

• List of investigational anxiolytics
• Lidanserin