Department of Neurology, Sichuan Academy of Medical Sciences, Sichuan People's Hospital, Chengdu, Sichuan 610072, P.R. China.
Mol Med Rep. 2018 Apr;17(4):6002-6008. doi: 10.3892/mmr.2018.8595. Epub 2018 Feb 13.
Cranial nerve involvement frequently involves neuron damage and often leads to psychiatric disorder caused by multiple inducements. Lurasidone is a novel antipsychotic agent approved for the treatment of cranial nerve involvement and a number of mental health conditions in several countries. In the present study, the neuroprotective effect of lurasidone by antagonist activities on histamine was investigated in a rat model of cranial nerve involvement. The antagonist activities of lurasidone on serotonin 5‑HT7, serotonin 5‑HT2A, serotonin 5‑HT1A and serotonin 5‑HT6 were analyzed, and the preclinical therapeutic effects of lurasidone were examined in a rat model of cranial nerve involvement. The safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lurasidone were also assessed in the cranial nerve involvement model. The therapeutic dose of lurasidone was 0.32 mg once daily, administered continuously in 14‑day cycles. The results of the present study found that the preclinical prescriptions induced positive behavioral responses following treatment with lurasidone. The MTD was identified as a once daily administration of 0.32 mg lurasidone. Long‑term treatment with lurasidone for cranial nerve involvement was shown to improve the therapeutic effects and reduce anxiety in the experimental rats. In addition, treatment with lurasidone did not affect body weight. The expression of the language competence protein, Forkhead‑BOX P2, was increased, and the levels of neuroprotective SxIP motif and microtubule end‑binding protein were increased in the hippocampal cells of rats with cranial nerve involvement treated with lurasidone. Lurasidone therapy reinforced memory capability and decreased anxiety. Taken together, lurasidone treatment appeared to protect against language disturbances associated with negative and cognitive impairment in the rat model of cranial nerve involvement, providing a basis for its use in the clinical treatment of patients with cranial nerve involvement.
颅神经受累常涉及神经元损伤，并常导致多种诱因引起的精神障碍。鲁拉西酮是一种新型抗精神病药物，已在多个国家批准用于治疗颅神经受累和多种精神健康状况。在本研究中，通过组胺拮抗剂活性研究了鲁拉西酮在颅神经受累大鼠模型中的神经保护作用。分析了鲁拉西酮对 5-羟色胺 5-HT7、5-HT2A、5-HT1A 和 5-HT6 的拮抗剂活性，并在颅神经受累大鼠模型中研究了鲁拉西酮的临床前治疗效果。还在颅神经受累模型中评估了鲁拉西酮的安全性、最大耐受剂量（MTD）和初步抗肿瘤活性。鲁拉西酮的治疗剂量为 0.32mg，每日一次，连续 14 天给药。本研究结果发现，临床前处方在给予鲁拉西酮后诱导出阳性行为反应。MTD 被确定为每日一次给予 0.32mg 鲁拉西酮。长期治疗颅神经受累可改善实验大鼠的治疗效果并减轻焦虑。此外，鲁拉西酮治疗不会影响体重。语言能力蛋白叉头框 P2 的表达增加，鲁拉西酮治疗的颅神经受累大鼠海马细胞中的神经保护 SxIP 基序和微管末端结合蛋白水平增加。鲁拉西酮治疗增强了记忆能力并降低了焦虑。总之，鲁拉西酮治疗似乎可预防与颅神经受累大鼠模型中负面和认知障碍相关的语言障碍，为其在颅神经受累患者的临床治疗中的应用提供了依据。
