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: Robert E Davis, Christoph U Correll
• Journal: Expert review of neurotherapeutics (Expert Rev Neurother) Vol. 16 Issue 6 Pg. 601-14 (06 2016) ISSN: 1744-8360 [Electronic] England
• PMID: 27042868 (Publication Type: Journal Article)

Chemical References

• Antipsychotic Agents
• Receptors, Dopamine D2
• Serotonin
• Dopamine

Topics

• Antipsychotic Agents (therapeutic use)
• Dopamine (metabolism)
• Humans
• Receptors, Dopamine D2
• Schizophrenia (drug therapy)
• Serotonin