Zhong Yongjie, Wang Wenhui, Zhang Miaomiao, Yao Yitan, Liu Huanzhong, Zhang Kai
Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China.
Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China.
Psychopharmacology (Berl). 2025 Mar;242(3):651-661. doi: 10.1007/s00213-024-06716-4. Epub 2024 Nov 18.
There is a debate about whether doctors should prophylactically use benzhexol in schizophrenic patients to reduce the occurrence of extrapyramidal side effects (EPS) after risperidone treatment.
We conducted a prospective animal model to explore the efficacy and safety of the prophylactic use of benzhexol after risperidone treatment and the mechanism of the process.
C57/BL mice were injected with MK-801 (0.5 mg/kg, i.p.) once a day for two weeks. The open field test (OFT) and the novel object recognition test (NORT) assessed the schizophrenia-like behavior of mice. After four weeks of treatment with benzhexol (10 mg/kg, i.g.) and risperidone (3 mg/kg, i.g.), the inclined screen test (IST), rotarod test (RT), open field test (OFT), novel object recognition test (NORT) and the Morris water maze test (MWM) were conducted successively. The expression of BDNF, p-Tau, and Tau in the hippocampus was detected by Western blot assay.
We showed that benzhexol can significantly attenuate risperidone-induced motor coordination impairments and catalepsy and did not affect the efficacy of risperidone in reducing spontaneous activity. Notably, the prophylactic use of benzhexol reduced the recognition memory and spatial memory in MK-801-induced model mice after risperidone. In addition, benzhexol increased the ratio of p-Tau/Tau and decreased BDNF expression levels in the hippocampus.
We found that the prophylactic use of benzhexol can reduce the occurrence of EPS and does not affect the efficacy of risperidone in the treatment of positive symptoms. Benzhexol may impair cognitive function but did not cause further deterioration of cognitive function in MK-801 mice.
对于医生是否应在精神分裂症患者中预防性使用苯海索以减少利培酮治疗后锥体外系副作用（EPS）的发生存在争议。
我们进行了一项前瞻性动物模型研究，以探讨利培酮治疗后预防性使用苯海索的疗效和安全性以及该过程的机制。
C57/BL小鼠每天腹腔注射一次MK-801（0.5毫克/千克），持续两周。旷场试验（OFT）和新物体识别试验（NORT）评估小鼠的精神分裂症样行为。在用苯海索（10毫克/千克，灌胃）和利培酮（3毫克/千克，灌胃）治疗四周后，依次进行倾斜屏幕试验（IST）、转棒试验（RT）、旷场试验（OFT）、新物体识别试验（NORT）和莫里斯水迷宫试验（MWM）。通过蛋白质免疫印迹法检测海马中脑源性神经营养因子（BDNF）、磷酸化tau蛋白（p-Tau）和tau蛋白（Tau）的表达。
我们发现苯海索可显著减轻利培酮诱导的运动协调障碍和僵住症，且不影响利培酮降低自发活动的疗效。值得注意的是，预防性使用苯海索会降低利培酮治疗后MK-801诱导的模型小鼠的识别记忆和空间记忆。此外，苯海索增加了海马中p-Tau/Tau的比例并降低了BDNF的表达水平。
我们发现预防性使用苯海索可减少EPS的发生，且不影响利培酮治疗阳性症状的疗效。苯海索可能会损害认知功能，但不会导致MK-801小鼠的认知功能进一步恶化。
