Lurasidone: a new drug in development for schizophrenia.
BACKGROUND
Lurasidone is a novel psychotropic agent in development for the treatment of schizophrenia and bipolar disorder.


OBJECTIVE
This paper describes the development of lurasidone, including its receptor binding affinities, pharmacokinetics, CNS activity in rodent models and results of early clinical efficacy and safety studies in humans.


METHODS
The available literature on lurasidone was reviewed, including abstracts from medical congresses supplemented by data on file with the sponsor.


CONCLUSIONS
Lurasidone has a high affinity for dopamine D(2) and serotonin 5-HT(2A) receptors as well as for receptors implicated in enhancement of cognitive function (e.g., 5-HT(7,) 5-HT(1A), alpha(2c)). Lurasidone has no affinity for muscarinic M(1) and histamine H(1) receptors and minimal affinity for alpha(1) adrenoceptors, dopamine D(1) and D(3) receptors, serotonin 5-HT(2C) receptors and alpha(2A) adrenoceptors. Phase II efficacy data indicate that lurasidone doses from 40 to 120 mg/day are effective in the treatment of schizophrenia, with positive symptom reduction exceeding that for negative symptoms, as seen with other antipsychotics. Preclinical data indicate that lurasidone reverses MK-801 induced learning and memory impairment in rodents, and active comparator data from a Phase Ib study of lurasidone 120 mg/day versus ziprasidone 160 mg/day also found a signal for effects on cognition. Phase II studies suggest that lurasidone has no significant QTc prolongation and a benign metabolic profile.
Meyer
Jonathan M
JM
Department of Psychiatry, University of California, San Diego, CA 92161, USA. jmmeyer@ucsd.edu
Loebel
Antony D
AD
Schweizer
Edward
E
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000503:physiopathology; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D054833:Isoindoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000069056:Lurasidone Hydrochloride; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D054833:Isoindoles; D013844:Thiazoles; D000069056:Lurasidone Hydrochloride