Bassant M H, Jazat-Poindessous F, Lamour Y
INSERM U 161, Paris, France.
J Cereb Blood Flow Metab. 1996 Sep;16(5):1014-25. doi: 10.1097/00004647-199609000-00027.
The effects of the centrally acting anti-cholinesterase metrifonate (MFT) and its metabolite dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) on local cerebral glucose utilization (LCGU) have been studied in 3- and 27-month-old rats, using the autoradiographic [14C]deoxyglucose technique. In 3-month-old rats, MFT (80 mg/kg i.p.) increased LCGU significantly in 17 of the 54 regions studied, including insular, cingulate, and temporal cortices, ventral hippocampus, thalamus, lateral habenula, substantia nigra, and superior colliculus. In these regions, the average MFT-induced increase in LCGU was 23% above control. The average hemispheric LCGU increased by 10% (p < 0.01). DDVP (5 mg/kg) increased LCGU in 19 regions (average increase 26%). The average hemispheric LCGU increased by 9% (p < 0.01). Regional distributions of MFT- and DDVP-induced increases in LCGU were similar and overlapped the distribution of the acetylcholinesterase activity. In 27-month-old rats, MFT was active in 18 regions (average increase 25%). The whole-brain mean LCGU increased by 10% (p < 0.01). MFT compensated for the age-related hypometabolism in some brain areas including insular, temporal, and retrosplenial cortices, substantia nigra, and superior colliculus. The effects of MFT on LCGU were preserved in old rats, at variance with other anticholinesterases (tacrine, physostigmine). Which are less active in the aged rat brain.
采用放射自显影[¹⁴C]脱氧葡萄糖技术，研究了中枢作用抗胆碱酯酶敌百虫（MFT）及其代谢产物敌敌畏（2,2-二氯乙烯基二甲基磷酸酯；DDVP）对3月龄和27月龄大鼠局部脑葡萄糖利用（LCGU）的影响。在3月龄大鼠中，MFT（80mg/kg腹腔注射）使所研究的54个区域中的17个区域的LCGU显著增加，包括岛叶、扣带回和颞叶皮质、腹侧海马、丘脑、外侧缰核、黑质和上丘。在这些区域，MFT诱导的LCGU平均增加比对照高23%。平均半球LCGU增加了10%（p<0.01）。DDVP（5mg/kg）使19个区域的LCGU增加（平均增加26%）。平均半球LCGU增加了9%（p<0.01）。MFT和DDVP诱导的LCGU增加的区域分布相似，且与乙酰胆碱酯酶活性分布重叠。在27月龄大鼠中，MFT在18个区域有活性（平均增加25%）。全脑平均LCGU增加了10%（p<0.01）。MFT补偿了一些脑区与年龄相关的代谢减退，这些脑区包括岛叶、颞叶和压后皮质、黑质和上丘。MFT对LCGU的影响在老年大鼠中得以保留，这与其他抗胆碱酯酶（他克林、毒扁豆碱）不同，其他抗胆碱酯酶在老年大鼠脑中活性较低。
