Disease relevance of Iloperidone

• Iloperidone was substantially less active in models of extrapyramidal side effect (EPS) liability, such as preventing apomorphine-induced stereotypy and causing catalepsy in rats [1].
• In patients treated with iloperidone, a low incidence of extrapyramidal symptoms and weight gain has been shown [2].

Psychiatry related information on Iloperidone

• The affinity for this particular set of receptors indicates that iloperidone has the potential to be a broad spectrum antipsychotic, with efficacy against positive, negative, depressive and cognitive symptoms of schizophrenia, and a low propensity to induce side effects [3].
• Based on the significant increase in the open arm time seen after iloperidone treatment in the elevated plus maze assay and increased interaction score in social interaction, iloperidone may also have favorable effects in the clinic on anxiety and, possibly, negative symptoms [1].
• In vivo, iloperidone antagonized apomorphine-induced climbing behavior in mice at low doses with good oral bioavailability, prevented 5-HT-induced head twitch in rats at low doses, and inhibited self-stimulation behavior in rats, pole climb avoidance in rats and continuous Sidman avoidance responding in monkeys [1].
• Iloperidone is a novel atypical antipsychotic compound currently under clinical development for the treatment of psychotic disorders [4].

High impact information on Iloperidone

• 3-[[(Aryloxy)alkyl]piperidinyl]-1,2-benzisoxazoles as D2/5-HT2 antagonists with potential atypical antipsychotic activity: antipsychotic profile of iloperidone (HP 873) [5].
• The mode of action of the antipsychotic drugs clozapine, haloperidol and iloperidone was investigated in layer V of prefrontal cortex slices using extracellular field potential, intracellular sharp-electrode as well as whole-cell voltage clamp recording techniques [6].
• Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone [7].
• Iloperidone (10 mg/kg) and melperone (10 mg/kg), but not quetiapine (30 mg/kg), produced an equivalent or a smaller increase in DA release in the nucleus accumbens (NAC), respectively, compared to the mPFC, whereas none of them increased ACh release in the NAC [8].
• Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic [9].

Chemical compound and disease context of Iloperidone

• Aripiprazole (tablets) and iloperidone (tablets and depot injection) are two antipsychotics in development for schizophrenia/schizoaffective disorder (available information regarding iloperidone is very limited) [10].

Biological context of Iloperidone

• Two studies on iloperidone evaluated its safety and tolerability, made a preliminary pharmacokinetic assessment of single 3- and 5-mg doses, and determined the effect of food on its tolerability and pharmacokinetics in healthy volunteers after single 3-mg doses [9].
• Hydroxylation of iloperidone produced 1(-)[4(-)[3(-)[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-2-hydroxy-5-methoxyphenyl]ethanone and 1(-)[4(-)[3(-)[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-3 -methoxyphenyl]propoxy]-2-hydroxyethanone, the later of which was found to be the principal metabolite in dogs [11].

Anatomical context of Iloperidone

• The metabolism of iloperidone was studied in human liver microsomes to define the metabolic pathways and to identify the cytochrome P450 (CYP) isoforms responsible for the formation of major iloperidone metabolites [7].
• In this study, the agonist/antagonist activity of iloperidone was determined in cell lines expressing recombinant human D(2A), D(3), alpha(2C), 5-HT(1A), or 5-HT(6) receptors [12].
• Given this affinity profile, and the observation that P95-12113 does not readily cross the blood-brain barrier, it is unlikely that this metabolite contributes to the therapeutic effect of iloperidone in patients with schizophrenia [4].

Associations of Iloperidone with other chemical compounds

• Iloperidone ¿HP 873: 1-[4-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1-piperidinyl]propoxy] -3-methoxyphenyl]ethanone¿ is a dopamine (D2)/serotonin (5-HT2) receptor antagonist with the preclinical profile of an atypical antipsychotic based on biochemical studies in rats [13].

Gene context of Iloperidone

• Functional characterization of the novel antipsychotic iloperidone at human D2, D3, alpha 2C, 5-HT6, and 5-HT1A receptors [12].
• Iloperidone (HP-873) is a 5-HT2 antagonist from Hoechst Marion Roussel Inc in clinical trials for the treatment of schizophrenia and psychosis [14].

Analytical, diagnostic and therapeutic context of Iloperidone

• Clinical trials are under way of the use of iloperidone for the treatment of schizophrenia [1].
• Iloperidone (1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone) demonstrated a potent antipsychotic profile in several in vitro and in vivo animal models [1].

References