Kumari Kusum, Kumar Sonu, Sinha Ritesh K, Toppo Mary Sunita
Pharmacology, Rajendra Institute of Medical Sciences, Ranchi, IND.
Pharmacology and Therapeutics, Rajendra Institute of Medical Sciences, Ranchi, IND.
Cureus. 2023 Jul 7;15(7):e41495. doi: 10.7759/cureus.41495. eCollection 2023 Jul.
Background Dementia is an age-related gradual loss of memory that is progressive in nature. Presently, the most common cause of dementia is Alzheimer's disease (AD), which is treated with donepezil, an anticholinesterase. But it only provides short-term symptomatic improvement. Liraglutide, which is an anti-diabetic drug, stimulates the anti-apoptotic pathway of nerve damage, which helps in regenerating nerve cells; so, it may help in dementia cases. Therefore, this study aimed to explore the effect of liraglutide on learning and memory and to compare its effect with donepezil in diazepam-induced amnesic albino rats. Methodology Twenty healthy male Albino rats weighing 150-200 grams were taken and divided into four groups: A, B, C, and D. Group A rats were normal rats, whereas the rats in groups B, C, and D were made amnesic by the intraperitoneal (i.p.) administration of 0.1 mg per kg of diazepam. Immediately after producing amnesia, group B rats received normal saline, group C received liraglutide, and group D received donepezil through the intraperitoneal route as test drugs. Group A rats received only normal saline. The amnesic effect was measured by the escape latency period, which was measured by using a Morris Water Maize (MWM) instrument. Escape latency is the time (in seconds) to locate the platform from the starting point. The amnesic effect is shown by an increase in escape latency and the anti-amnesic effect by a decrease in escape latency. Escape latency was recorded at 0 hr, 1 hr, 2 hr, 3 hr, and 4 hr after test drug administration. Results Group B rats showed an increase in escape latency, which shows the amnesic effect of diazepam. When group C and group D amnesic rats were treated with liraglutide and donepezil, respectively, a one-hour after-treatment increase in escape latency was seen but after two hours, both groups showed a decrease in escape latency, which indicates the anti-amnesic effect of both drugs. When groups C and D were compared, and the post-hoc highly significant difference (HSD) test was used, there was no significant difference between the two drugs, although the liraglutide-treated group (C) showed a lower anti-amnesic effect. However, group C showed a significant effect as compared to group B rats (p-value <0.05), which indicates the anti-amnesic property of liraglutide as compared to normal saline. Conclusion Liraglutide shows an anti-amnesic property. Since it works by a mechanism different from donepezil, it can be used as add-on therapy with donepezil in dementia patients.
痴呆是一种与年龄相关的渐进性记忆力减退。目前，痴呆最常见的病因是阿尔茨海默病（AD），可用抗胆碱酯酶药物多奈哌齐进行治疗。但它只能提供短期的症状改善。利拉鲁肽是一种抗糖尿病药物，可刺激神经损伤的抗凋亡途径，有助于神经细胞再生；因此，它可能对痴呆病例有帮助。因此，本研究旨在探讨利拉鲁肽对学习和记忆的影响，并在地西泮诱导的失忆白化大鼠中比较其与多奈哌齐的效果。
选取20只体重150 - 200克的健康雄性白化大鼠，分为四组：A、B、C和D组。A组大鼠为正常大鼠，而B、C和D组大鼠通过腹腔注射每千克0.1毫克地西泮使其失忆。失忆产生后，B组大鼠立即接受生理盐水，C组接受利拉鲁肽，D组接受多奈哌齐作为受试药物，通过腹腔途径给药。A组大鼠仅接受生理盐水。失忆效果通过逃避潜伏期来衡量，使用莫里斯水迷宫（MWM）仪器进行测量。逃避潜伏期是指从起点找到平台所需的时间（以秒为单位）。逃避潜伏期增加表明失忆效果，逃避潜伏期减少表明抗失忆效果。在给药后0小时、1小时、2小时、3小时和4小时记录逃避潜伏期。
B组大鼠逃避潜伏期增加，表明地西泮的失忆效果。当C组和D组失忆大鼠分别用利拉鲁肽和多奈哌齐治疗时，治疗后1小时逃避潜伏期增加，但2小时后，两组逃避潜伏期均减少，这表明两种药物都有抗失忆效果。当比较C组和D组，并使用事后高度显著差异（HSD）检验时，两种药物之间没有显著差异，尽管利拉鲁肽治疗组（C组）的抗失忆效果较低。然而，与B组大鼠相比，C组显示出显著效果（p值<0.05），这表明与生理盐水相比，利拉鲁肽具有抗失忆特性。
利拉鲁肽具有抗失忆特性。由于其作用机制与多奈哌齐不同，它可作为多奈哌齐的辅助治疗药物用于痴呆患者。
