BACKGROUND: Lurasidone is a novel psychotropic agent in development for the treatment of schizophrenia and bipolar disorder. OBJECTIVES: 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. RESULTS/ 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.
BACKGROUND:Lurasidone is a novel psychotropic agent in development for the treatment of schizophrenia and bipolar disorder. OBJECTIVES: 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. RESULTS/ 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.
Authors: Dean F Wong; Hiroto Kuwabara; James Robert Brašić; Thomas Stock; Atul Maini; Emily G Gean; Antony Loebel Journal: Psychopharmacology (Berl) Date: 2013-05-07 Impact factor: 4.530
Authors: Masakuni Horiguchi; Kayleen E Hannaway; Adesewa E Adelekun; Karu Jayathilake; Herbert Y Meltzer Journal: Neuropsychopharmacology Date: 2012-06-27 Impact factor: 7.853