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[摘要]：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-HT2A receptors as well as for receptors implicated in enhancement of cognitive function (e.g., 5-HT7, 5-HT1A, 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-HT2C 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. |
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