Scali C, Giovannini M G, Bartolini L, Prosperi C, Hinz V, Schmidt B, Pepeu G
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Eur J Pharmacol. 1997 May 1;325(2-3):173-80. doi: 10.1016/s0014-2999(97)00128-3.
The effects of metrifonate were investigated in 4-6- and 22-24-month-old rats. Extracellular acetylcholine levels were measured by transversal microdialysis in vivo. Baseline extracellular acetylcholine levels in the cerebral cortex and hippocampus were 42% and 60% lower, respectively, in old than in young rats. Old rats did not discriminate between familiar and novel objects. In old rats, metrifonate (80 mg/kg p.o.) brought about 85% inhibition of cholinesterase activity in the cortex and hippocampus, a 4-fold increase in extracellular acetylcholine levels in the cortex only, and restored object recognition. In young rats, metrifonate caused 75% cholinesterase inhibition in the cerebral cortex and hippocampus, a 2-fold increase in cortical and hippocampal extracellular acetylcholine levels, and no effect on object recognition. The slight cholinesterase inhibition following metrifonate (30 mg/kg) in aged rats had no effect on cortical acetylcholine levels and object recognition. In conclusion, metrifonate may improve the age-associated cholinergic hypofunction and cognitive impairment.
研究了敌百虫对4至6月龄和22至24月龄大鼠的影响。通过横向微透析在体内测量细胞外乙酰胆碱水平。老年大鼠大脑皮层和海马体的细胞外乙酰胆碱基线水平分别比年轻大鼠低42%和60%。老年大鼠无法区分熟悉和新颖的物体。在老年大鼠中，敌百虫（口服80mg/kg）导致皮层和海马体中胆碱酯酶活性受到85%的抑制，仅使皮层中的细胞外乙酰胆碱水平增加4倍，并恢复了物体识别能力。在年轻大鼠中，敌百虫导致大脑皮层和海马体中75%的胆碱酯酶抑制，皮层和海马体中的细胞外乙酰胆碱水平增加2倍，且对物体识别没有影响。老年大鼠服用敌百虫（30mg/kg）后轻微的胆碱酯酶抑制对皮层乙酰胆碱水平和物体识别没有影响。总之，敌百虫可能改善与年龄相关的胆碱能功能减退和认知障碍。
