新規統合失調症治療薬ルラシドン塩酸塩の創製: 構造活性相関•非臨床薬理評価

摘要

Lurasidone hydrochloride received approval by the FDA in 2010 for the treatment of schizophrenia. Lurasidone is a full antagonist at dopamine D2 and serotonin 5-HT_(2A) receptors, properties shared by most second-generation antipsychotics. Lurasidone also has high affinity for serotonin 5-HT_7 and is a partial agonist at 5-HT_(1A) receptors; it is believed that these properties could be potentially related to effects on cognition and mood. Of particular note is that lurasidone has minimal affinities for receptors that might induce adverse events. The low affinity for alpha-1 noradrenergic receptors predicts alower risk for orthostatic hypotension. Moreover the minimal affinity for 5-HT_(2C) receptors and histamine H_1 receptors predicts lower liability for weight gain as well. The lack of affinity for cholinergic M_1 receptors predicts alow propensity for anticholinergic side effects. Our attempts to reduce adverse events had enabled us to obtain lurasidone with better tolerability and efficacy. Here, we report the synthesis, structure and activity relationships and pharmacological profiles of lurasidone.%統合失調症は、一般人口の約1%に発症する精神疾患の一つである。厚生労働省の調査によると、統合失調症患者数は79.5万人にのぼる。入院を要する重症患者数は18.7万人、外来患者数は6.6万人である(2008年)。統合失調症の国内年間医療費は一兆円に達しており、疾患による社会的•経済的な損失の改善が急務となつている。