Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders

Author(s): Marianna Mazza*, Giuseppe Marano, Gianandrea Traversi, Gabriele Sani, Luigi Janiri

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 19 , Issue 4 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Lumateperone (ITI-007) is a tosylate salt with binding affinities to receptors implicated in the therapeutic actions of antipsychotic medications, including the serotonin 5HT2A receptors, dopamine D2 and D1 receptors and the serotonin transporter. It has a unique mechanism of action because it simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, implicated in serious mental illness. It can be considered a multi-target-directed ligand and a multifunctional modulator of serotoninergic system with possible precognitive, antipsychotic, antidepressant and anxiolytic properties. Lumateperone has been investigated as a novel agent for the treatment of schizophrenia, but it represents a new potential option for other psychiatric and neurological diseases, such as behavioural symptoms of dementia or Alzheimer’s disease, sleep disturbances, bipolar depression. Besides, it has demonstrated a favourable safety profile without significant extrapyramidal side effects, hyperprolactinemia or changes in cardiometabolic or endocrine factors versus placebo. Additional studies are warranted to confirm and examine the benefit of lumateperone and possible therapeutic targets. This paper is a comprehensive and thorough summary of the most important findings and potential future role of this particular compound in personalized treatments.

Keywords: Lumateperone, ITI-007, schizophrenia, Alzheimer`s disease, novel antipsychotics, personalized medicine.

Snyder GL, Vanover KE, Zhu H, et al. Functional profile of a novel modulator of serotonin, dopamine, and glutamate neurotransmission. Psychopharmacology (Berl) 2015; 232(3): 605-21.
[http://dx.doi.org/10.1007/s00213-014-3704-1] [PMID: 25120104]
Vanover KE, Davis RE, Zhou Y, et al. Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. Neuropsychopharmacology 2019; 44(3): 598-605.
[http://dx.doi.org/10.1038/s41386-018-0251-1] [PMID: 30449883]
Ibarra A, Mendieta-Arbesú E, Suarez-Meade P, et al. Motor recovery after chronic spinal cord transection in rats: a proof-of-concept study evaluating a combined strategy. CNS Neurol Disord Drug Targets 2019; 18(1): 52-62.
[http://dx.doi.org/10.2174/1871527317666181105101756] [PMID: 30394222]
Raj K, Chawla P, Singh S. Neurological disorders associated to long term tramadol utilization: pathological mechanisms and future perspective. CNS Neurol Disord Drug Targets 2019. epub ahead of print
Guzmán DC, Brizuela NO, Herrera MO, et al. Cytarabine and ferric carboxymaltose (Fe+3) increase oxidative damage and alter serotonergic metabolism in brain. CNS Neurol Disord Drug Targets 2019; 18(2): 149-55.
[http://dx.doi.org/10.2174/1871527318666181128144343] [PMID: 30484410]
Miri AL, Hosni AP, Gomes JC, et al. Study of the effects of L-tryptophane nanoparticles on motor behavior in Alzheimer’s experimental models. CNS Neurol Disord Drug Targets 2019; 18(1): 44-51.
[http://dx.doi.org/10.2174/1871527317666181105111157] [PMID: 30394223]
de Oliveira DR, da Silva DM, Florentino IF, et al. Monoamine involvement in the antidepressant-like effect of β-caryophyllene. CNS Neurol Disord Drug Targets 2018; 17(4): 309-20.
[http://dx.doi.org/10.2174/1871527317666180420150249] [PMID: 29676236]
Sahlholm K, Valle-Leon M, Taura J, Fernandez-Duenas V, Ciruela F. Effects of the dopamine stabilizer, pridopidine, on basal and phencyclidine-induced locomotion: role of dopamine D2 and sigma-1 receptors. CNS Neurol Disord Drug Targets 2018; 17(7): 522-7.
[http://dx.doi.org/10.2174/1871527317666180627103337] [PMID: 29952269]
Seyedi M, Gholami F, Samadi M, et al. The effect of vitamin D3 supplementation on serum BDNF, dopamine, and serotonin in children with attention-deficit/hyperactivity disorder. CNS Neurol Disord Drug Targets 2019; 18(6): 496-501.
[http://dx.doi.org/10.2174/1871527318666190703103709] [PMID: 31269890]
Ormstad H, Bryn V, Verkerk R, et al. Serum tryptophan, tryptophan catabolites and brain-derived neurotrophic factor in subgroups of youngsters with autism spectrum disorders. CNS Neurol Disord Drug Targets 2018; 17(8): 626-39.
[http://dx.doi.org/10.2174/1871527317666180720163221] [PMID: 30033880]
Davis RE, Vanover KE, Zhou Y, et al. ITI-007 demonstrates brain occupancy at serotonin 5-HT2A and dopamine D2 receptors and serotonin transporters using positron emission tomography in healthy volunteers. Psychopharmacology (Berl) 2015; 232(15): 2863-72.
[http://dx.doi.org/10.1007/s00213-015-3922-1] [PMID: 25843749]
Lieberman JA, Davis RE, Correll CU, et al. ITI-007 for the treatment of schizophrenia: a 4-week randomized, double-blind, controlled trial. Biol Psychiatry 2016; 79(12): 952-61.
[http://dx.doi.org/10.1016/j.biopsych.2015.08.026] [PMID: 26444072]
Corponi F, Fabbri C, Bitter I, et al. Novel antipsychotics specificity profile: a clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone. Eur Neuropsychopharmacol 2019; 29(9): 1061-2.
[http://dx.doi.org/10.1016/j.euroneuro.2019.07.001] [PMID: 31371104]
Krogmann A, Peters L, von Hardenberg L, Bödeker K, Nöhles VB, Correll CU. Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. CNS Spectr 2019; 24(S1): 38-69.
[http://dx.doi.org/10.1017/S109285291900124X] [PMID: 31482779]
Wang SM, Han C, Lee SJ, et al. Investigational dopamine antagonists for the treatment of schizophrenia. Expert Opin Investig Drugs 2017; 26(6): 687-98.
[http://dx.doi.org/10.1080/13543784.2017.1323870] [PMID: 28443355]
Mazza M, Marano G, Traversi G, Carocci V, Romano B, Janiri L. Cariprazine in bipolar depression and mania: state of the art. CNS Neurol Disord Drug Targets 2018; 17(10): 723-7.
[http://dx.doi.org/10.2174/1871527317666180828120256] [PMID: 30152291]
Citrome L. Emerging pharmacological therapies in schizophrenia: what’s new, what’s different, what’s next? CNS Spectr 2016; 21(S1): 1-12.
[http://dx.doi.org/10.1017/S1092852916000729] [PMID: 28044942]
Davis RE, Correll CU. ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical outcomes. Expert Rev Neurother 2016; 16(6): 601-14.
[http://dx.doi.org/10.1080/14737175.2016.1174577] [PMID: 27042868]
Correll CU, Davis RE, Weingart M, et al. Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical trial. JAMA Psychiatry 2020. Epub ahead of print
[http://dx.doi.org/10.1001/jamapsychiatry.2019.4379] [PMID: 31913424]
Blair HA. Lumateperone: First Approval. Drugs 2020; 80(4): 417-23.
[http://dx.doi.org/10.1007/s40265-020-01271-6] [PMID: 32060882]
Corponi F, Fabbri C, Bitter I, et al. Novel antipsychotics specificity profile: a clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone. Eur Neuropsychopharmacol 2019; 29(9): 971-85.
[http://dx.doi.org/10.1016/j.euroneuro.2019.06.008] [PMID: 31255396]
Vyas P, Hwang BJ, Brasic JR. An evaluation of lumateperone tosylate for the treatment of schizophrenia. Expert Opin Pharmacother 2019; 30: 1-7.
[PMID: 31790322]
Snyder GL, Vanover KE. Intracellular signaling and approaches to the treatment of schizophrenia and associated cognitive impairment. Curr Pharm Des 2014; 20(31): 5093-103.
[http://dx.doi.org/10.2174/1381612819666131216115417] [PMID: 24345266]
Porsteinsson AP, Antonsdottir IM. An update on the advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother 2017; 18(6): 611-20.
[http://dx.doi.org/10.1080/14656566.2017.1307340] [PMID: 28300462]
Calsolaro V, Antognoli R, Okoye C, Monzani F. The use of antipsychotic drugs for treating behavioral symptoms in Alzheimer’s disease. Front Pharmacol 2019; 10: 1465.
[http://dx.doi.org/10.3389/fphar.2019.01465] [PMID: 31920655]
Ahmed M, Malik M, Teselink J, Lanctôt KL, Herrmann N. Current agents in development for treating behavioral and psychological symptoms associated with dementia. Drugs Aging 2019; 36(7): 589-605.
[http://dx.doi.org/10.1007/s40266-019-00668-7] [PMID: 30957198]
Jankowska A, Wesolowska A, Pawlowski M, Chlon-Rzepa G. Multi-target-directed ligands affecting serotonergic neurotransmission for Alzheimer’s disease therapy: advances in chemical and biological research. Curr Med Chem 2018; 25(17): 2045-67.
[http://dx.doi.org/10.2174/0929867324666170529122802] [PMID: 28554324]
Zisapel N. Current phase II investigational therapies for insomnia. Expert Opin Investig Drugs 2015; 24(3): 401-11.
[http://dx.doi.org/10.1517/13543784.2015.987340] [PMID: 25423562]
Li P, Zhang Q, Robichaud AJ, et al. Discovery of a tetracyclic quinoxaline derivative as a potent and orally active multifunctional drug candidate for the treatment of neuropsychiatric and neurological disorders. J Med Chem 2014; 57(6): 2670-82.
[http://dx.doi.org/10.1021/jm401958n] [PMID: 24559051]
Kumar B, Kuhad A, Kuhad A. Lumateperone: a new treatment approach for neuropsychiatric disorders. Drugs Today (Barc) 2018; 54(12): 713-9.
[http://dx.doi.org/10.1358/dot.2018.54.12.2899443] [PMID: 30596390]
Kantrowitz JT. The potential role of lumateperone-something borrowed? something new? JAMA Psychiatry 2020. [Epub ahead of print]
[http://dx.doi.org/10.1001/jamapsychiatry.2019.4265] [PMID: 31913409]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [243 - 247]
Pages: 5
DOI: 10.2174/1871527319666200601145653
Price: $65

Article Metrics

PDF: 50