title: ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical outcomes.
abstract: ITI-007 is an investigational drug being developed for schizophrenia and other neuropsychiatric/neurodegenerative diseases. ITI-007 has a unique pharmacological profile, combining potent 5-HT2a receptor antagonism with cell-type-specific dopamine and glutamate receptor modulation, plus serotonin reuptake inhibition. At dopamine-D2 receptors, ITI-007 acts as a post-synaptic antagonist and pre-synaptic partial agonist. Additionally, ITI-007 stimulates phosphorylation of glutamatergic NMDA-NR2B receptors, downstream of dopamine-D1 receptor intracellular signaling. Based on a large, placebo and risperidone controlled, Phase-II trial, ITI-007 60 mg was shown to be effective in reducing symptoms in patients with acutely exacerbated schizophrenia. The antipsychotic efficacy of ITI-007 60 mg in this patient population was confirmed in a recently completed Phase III study. ITI-007 was associated with minimal safety risk compared to risperidone (Phase II study) or placebo (both studies) for neuromotor disturbances, prolactin changes, weight gain and metabolic abnormalities. A second 6-week, placebo and risperidone-controlled Phase-III trial in acutely exacerbated schizophrenia is ongoing.
authors.affiliation: a 3-D Pharmaceutical Consultants Inc ., San Diego , CA , USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Davis
authors.affiliation: b Department of Psychiatry , Northwell Health, The Zucker Hillside Hospital , Glen Oaks , NY , USA.|c Hofstra Northwell School of Medicine , Hempstead , NY , USA.|d The Feinstein Institute for Medical Research , Manhasset , NY , USA.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D017448:Receptors, Dopamine D2; D012559:Schizophrenia / Q000188:drug therapy*; D012701:Serotonin
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D012701:Serotonin; D004298:Dopamine
keywords: 5HT2a receptors; Antipsychotic; NMDA receptors; dopamine D2 receptors; dopamine receptor phosphoprotein modulator; efficacy; neuropsychiatric disorders; safety; schizophrenia; serotonin reuptake transporter