Fujii T, Kuraishi Y, Ueda M, Satoh M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Neuropharmacology. 1991 Dec;30(12A):1291-5. doi: 10.1016/0028-3908(91)90025-7.
Bifemelane has an anti-amnesic effect, produces the translocation of protein kinase C in the hippocampal CA3 region but not in CA1 and enhances long-term potentiation in the mossy fibre-CA3 system but not in the Schaffer collateral-CA1 system. The present study examined the specific binding of [3H]bifemelane in membrane preparations of guinea pig hippocampus and regional differences in such a binding. The binding of [3H]bifemelane was reversible and greater when incubated at 4 degrees C than at 25 or 37 degrees C. The binding of [3H]bifemelane appeared to be composed of at least 2 different affinity components. Imipramine significantly suppressed the binding of [3H]bifemelane at 1 microM and, in the presence of 1 microM imipramine, the low-affinity component of the binding of [3H]bifemelane was eliminated. The density of specific binding sites for 1 nM [3H]bifemelane was significantly higher in the hippocampal CA3 region than in the CA1. The specific binding of 1 nM [3H]bifemelane was not inhibited by other nootropic drugs, such as idebenone, calcium hopantenate, vinpocetine, indeloxazine and piracetam. The present results suggest that there are specific binding sites for bifemelane in hippocampus, which are different from those for other nootropic drugs tested and that the regional differences in the pharmacological susceptibilities to bifemelane are at least, in part, attributed to those in the density of binding sites for bifemelane.
双苯美仑具有抗遗忘作用，可使海马CA3区而非CA1区的蛋白激酶C发生转位，并增强苔藓纤维-CA3系统而非Schaffer侧支-CA1系统的长时程增强。本研究检测了[3H]双苯美仑在豚鼠海马膜制剂中的特异性结合以及这种结合的区域差异。[3H]双苯美仑的结合是可逆的，在4℃孵育时比在25℃或37℃时更强。[3H]双苯美仑的结合似乎由至少2种不同亲和力的成分组成。丙咪嗪在1μM时可显著抑制[3H]双苯美仑的结合，并且在存在1μM丙咪嗪的情况下，[3H]双苯美仑结合的低亲和力成分被消除。1nM[3H]双苯美仑特异性结合位点的密度在海马CA3区显著高于CA1区。1nM[3H]双苯美仑的特异性结合不受其他促智药物的抑制，如艾地苯醌、钙泛酸盐、长春西汀、茚洛秦和吡拉西坦。目前的结果表明，海马中存在双苯美仑的特异性结合位点，这些位点与所测试的其他促智药物的结合位点不同，并且双苯美仑药理学敏感性的区域差异至少部分归因于双苯美仑结合位点密度的差异。
