Kale Oluwafemi E, Awodele Olufunsho, Ogundare Temitope F, Ekor Martins
Department of Pharmacology, Benjamin Carson (Snr.) School of Medicine, Babcock University, Ilisan-Remo, Ogun State, 21244 Ikeja, Nigeria.
Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, University of Lagos, P.M.B 12003 Idi-Araba, Lagos, Nigeria.
Fundam Clin Pharmacol. 2017 Jun;31(3):329-339. doi: 10.1111/fcp.12267. Epub 2017 Feb 20.
This study investigated the modulatory and chemopreventive benefit of amlodipine (AML), a dihydropyridine calcium channel antagonist, against neurobehavioural abnormalities (NAs) associated with chlorpromazine (CPZ) toxicity in mice. Adult mice were divided into five groups of six animals/group. Group 1 (control) was administered saline (10 mL/kg i.p.). Group 2 received CPZ (2 mg/kg i.p.). Groups 3 and 4 received bromocriptine (BMC, 2.5 mg/kg s.c.) and AML (1 mg/kg s.c.), respectively, while group 5 received their combination. Groups 3-5 later received CPZ 30 min after initial treatments. Animals were subjected to neurobehavioural tests and euthanized 18 h later. CPZ-induced NAs were characterized by significant increase (P < 0.001) in cataleptic behaviour and lowered (P < 0.05) spontaneous activity reaction time in mice. There were also significant (P < 0.001) increases in malondialdehyde levels and decreased locomotion plus learning and memory parameters (P < 0.05-0.001). AML pretreatment alone did not alleviate CPZ-induced motor deficits in the mice. While pretreatment with BMC alone attenuated CPZ-associated catalepsy, its combination with AML further protected mice against NAs. Furthermore, BMC pretreatment did not affect CPZ-induced increase in malondialdehyde level, but AML or BMC+AML significantly (P < 0.05) decreased malondialdehyde in the CPZ-treated rats. Reduced glutathione levels and activities of superoxide dismutase and catalase remained elevated in all treatment groups. In conclusion, data from this study suggest possible chemopreventive benefit of AML alone or in combination with BMC against CPZ-associated neurobehavioural deficits. The ameliorative effect of AML may be related to its antioxidant and/or calcium channel blocking property.
本研究调查了二氢吡啶类钙通道拮抗剂氨氯地平（AML）对小鼠中与氯丙嗪（CPZ）毒性相关的神经行为异常（NA）的调节和化学预防作用。成年小鼠被分为五组，每组六只动物。第1组（对照组）腹腔注射生理盐水（10 mL/kg）。第2组接受CPZ（2 mg/kg腹腔注射）。第3组和第4组分别皮下注射溴隐亭（BMC，2.5 mg/kg）和AML（1 mg/kg），而第5组接受它们的组合。第3 - 5组在初始治疗30分钟后接受CPZ。对动物进行神经行为测试，并在18小时后实施安乐死。CPZ诱导的NA表现为小鼠僵住行为显著增加（P < 0.001），自发活动反应时间降低（P < 0.05）。丙二醛水平也显著增加（P < 0.001），运动以及学习和记忆参数降低（P < 0.05 - 0.001）。单独使用AML预处理并不能减轻CPZ诱导的小鼠运动缺陷。虽然单独使用BMC预处理可减轻与CPZ相关的僵住症，但其与AML联合使用能进一步保护小鼠免受NA影响。此外，BMC预处理并未影响CPZ诱导的丙二醛水平升高，但AML或BMC + AML可显著（P < 0.05）降低CPZ处理大鼠的丙二醛水平。所有治疗组的还原型谷胱甘肽水平以及超氧化物歧化酶和过氧化氢酶的活性均保持升高。总之，本研究数据表明AML单独或与BMC联合使用对CPZ相关神经行为缺陷可能具有化学预防作用。AML的改善作用可能与其抗氧化和/或钙通道阻断特性有关。
