ILOPERIDONE

Absorption

Well absorbed from the GI tract and Cmax is reached within 2-4 hours. Steady-state concentration is achieved in 3-4 days post-administration of iloperidone. Relative bioavailability of the tablet formulation compared to oral solution is 96%. Accumulation occurs in a predictable fashion.

Toxicity

Commonly observed adverse reactions (incidence ≥5% and two-fold greater than placebo) were: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased.

Description

Iloperidone is an atypical antipsychotic and adrenergic, dopamine, and serotonin (5-HT) receptor antagonist. It binds to several receptors, including the α₁-adrenergic receptor (α₁-AR), α₂-AR, and dopamine D₂ receptor (K_is = 0.31, 3, and 3.3 nM, respectively), as well as the 5-HT_1A, 5-HT_1D, 5-HT_2A, and 5-HT_2C receptors (K_is = 33, 15, 0.2, and 14 nM, respectively) in radioligand binding assays using human post-mortem brain tissue. Iloperidone also binds to human D₁, D₃, D₄, D₅, and rat 5-HT₂ receptors (K_is = 216, 7.1, 25, 319, and 3.1 nM, respectively, in CHO cells) and the histamine H₁ receptor (K_i = 12.3 nM in human post-mortem brain tissue). Iloperidone (1-3 mg/kg) prevents the reduction in prepulse inhibition induced by apomorphine , phencyclidine (PCP), and cirazoline in rats. It also increases the time rats spend in the open arms of the elevated plus maze and the number of social interactions when administered at a dose of 0.5 mg/kg. Formulations containing iloperidone have been used in the treatment of schizophrenia.

The Uses of ILOPERIDONE

Iloperidone (Fanapt, Fanapta, Zomaril) is an atypical antipsychotic for the treatment of schizophrenia. Iloperidone is a monoamine directed towards acting upon and antagonizing specific neurotransmitters, particularly multiple dopamine and serotonin recep

Indications

Treatment of acute schizophrenia.

Background

Iloperidone is an atypical antipsychotic for the treatment of schizophrenia symptoms. Hoechst Marion Roussel Inc. researched the drug until May 1996. In June 1997 they gave the research rights to Titan Pharmaceuticals, who gave the worldwide development, manufacturing, and marketing rights to Novartis in August 1998. On June 9, 2004, Titan Pharmaceuticals gave the Phase III development rights to Vanda Pharmaceuticals. FDA approved on May 9, 2009.

What are the applications of Application

Iloperidone is a dopamine (D2) and serotonin (5HT2) receptor antagonist

Pharmacokinetics

Iloperidone shows high affinity and maximal receptor occupancy for dopamine D2 receptors in the caudate nucleus and putamen of the brains of schizophrenic patients. The improvement in cognition is attributed to iloperidone's high affinity for α adrenergic receptors. Iloperidone also binds with high affinity to serotonin 5-HT2a and dopamine 3 receptors. Iloperidone binds with moderate affinity to dopamine D4, serotonin 5-HT6 and 5-HT7, and norepinephrine NEα1 receptors. Furthermore, iloperidone binds with weak affinity to serotonin 5-HT1A, dopamine D1, and histamine H1 receptors.

Metabolism

Iloperidone is hepatically metabolized by cytochrome enzymes which mediates O-dealkylation (CYP3A4), hydroxylation (CYP2D6), and decarboxylation/reduction processes. Metabolites formed are P89, P95, and P88. The minor metabolite is P89, whereas P95 and P88 are the major ones. The affinity of the iloperidone metabolite P88 is generally equal or less than that of the parent compound. In contrast, the metabolite P95 only shows affinity for 5-HT2A (Ki value of 3.91) and the NEα1A, NEα1B, NEα1D, and NEα2C receptors (Ki values of 4.7, 2.7, 8.8 and 4.7 nM respectively).