Salimzade Asma, Hosseini-Sharifabad Ali, Rabbani Mohammad
Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2017 Jun;12(3):204-210. doi: 10.4103/1735-5362.207201.
Memory impairment is one of the greatest concerns when it comes to long-term CNS-affecting drug administration. Drugs like gabapentin, pregabalin and baclofen are administered in a long-term period in conditions such as epilepsy, neuropathic pain, spasticity associated with spinal cord injury or multiple sclerosis. Despite their wide spread use, few data are available on the effects of these drugs on cognitive functions, such as learning memory. In the present study, the effects of long-term administration of gabapentin, pregabalin and baclofen on memory were investigated in a comparative manner. Male Wistar rats received intraperitoneal (i.p.) injection of gabapentin (30 mg/kg), pregabalin (30 mg/kg), baclofen (3 mg/kg), combination of gabapentin/baclofen (30/3 mg/kg) and combination of pregabalin/baclofen (30/3 mg/kg) once a day for 3 weeks respective to their groups. After the end of treatments, rat memories were assessed using the object-recognition task. The discrimination and recognition indices (RI and DI) in the T2 trials were used as the memory indicating factors. The results showed that daily i.p. administrations of pregabalin but not gabapentin or baclofen significantly decreased DI and RI compared to saline group. In combination groups, either gabapentin or pregabalin impaired discrimination between new and familiar objects. Our findings suggested that pregabalin alone or in combination with baclofen significantly caused cognitive deficits.
在长期使用影响中枢神经系统的药物时,记忆障碍是最令人担忧的问题之一。加巴喷丁、普瑞巴林和巴氯芬等药物常用于癫痫、神经性疼痛、脊髓损伤或多发性硬化症相关的痉挛等病症的长期治疗。尽管它们被广泛使用,但关于这些药物对认知功能(如学习记忆)影响的数据却很少。在本研究中,以比较的方式研究了加巴喷丁、普瑞巴林和巴氯芬长期给药对记忆的影响。雄性Wistar大鼠分别按组每天腹腔注射一次加巴喷丁(30毫克/千克)、普瑞巴林(30毫克/千克)、巴氯芬(3毫克/千克)、加巴喷丁/巴氯芬组合(30/3毫克/千克)和普瑞巴林/巴氯芬组合(30/3毫克/千克),持续3周。治疗结束后,使用物体识别任务评估大鼠的记忆。T2试验中的辨别和识别指数(RI和DI)用作记忆指示因素。结果表明,与生理盐水组相比,每天腹腔注射普瑞巴林可显著降低DI和RI,而加巴喷丁或巴氯芬则无此作用。在联合用药组中,加巴喷丁或普瑞巴林均损害了对新物体和熟悉物体的辨别能力。我们的研究结果表明,单独使用普瑞巴林或与巴氯芬联合使用均会显著导致认知缺陷。