神経ペプチドを指標とする脳循環代謝改善剤の作用特異性の解析

药物的一种变体，称为脑激活剂，在临床上用于与脑血管疾病、头部感染和其他有机脑激发症有关的多种症状体治疗。经典神经发射器对信号转导的刺激的影响已被建议在某些药物的药理学中。最近神经肽的作用被吸引为神经发射器/神经调节器。The present study aimed at distinctive caracterizing molecular basis of the pharmacological effects of such drugs with special reference to neuropeptides。第一，双氟醚羟基（BFM·HCI）和靛蓝羟基（IND·HCI），其中两个都希望有相同的临床影响，并对人体对神经肽、VIP和加兰素、大鼠大脑的影响进行了评估。Interperitoneal BFM·HCI和IND·HCI都改变了血管活性肽（VIP）和大鼠脑中的galanin in在tissue-特定人员。BFM·HCI显著增加了在Thalamus和hypothalamus中的贵宾内容，以及在Thalamus中的低聚糖集中度。在另一只手， IND·HCI和IND·HCI在大脑VIP上，以及加兰宁在两种药物的药理作用的分子机制中的明显差异。使用^2 H-BFM和大鼠脑合成体片段，在Thalamus中检测到了一个特定的绑定站点。^<14>C-IND发现了与各种大鼠脑组织相结合的片段进行交互。The binding of ^<14>C0IND was inhibited IND·HCI dose-dependently and no substantial differences were observed among the tissues examined。有趣的是， BFM·HCI， propranolol·HCI和imipramine-HCI也展示了IND绑定网站的基本相同亲和力的强度。这四种化合物共享一个部分结构，即-O-C-C-N-或与普通密切相关。这个绑定站点的重要性，因为它的药理学影响仍然可以被解释。

A variety of drugs, the so-called brain activators, are used clinically for the treatment of multiple symptoms related to cerebrovascular disease, head infury and other organic brain shyndromes. Implication of stimulation of signal tranmission by classical neurotransmitters has been suggested in pharmacologuy of some of those drugs. Recently the roles of neuropeptides have attracted attention as neurotransmitter/neuromodulator. The present study aimed at distinctive caracterizing molecular basis of the pharmacological effects of such drugs with special reference to neuropeptides. First, bifemelane hydrochloride (BFM・HCI) and indeloxazine hydrochloride (IND・HCI), both of which are expected to have the same clinical effects, were examined with respect to in vivo effects on nuropeptides, VIP and galanin, in rat brain. Interperitoneal BFM・HCI and IND・HCI both changed contents of vasoactive intestinal peptide (VIP) and galanin in rat brain in tissue-specific manners. BFM・HCI significantly raised VIP content in thalamus and hypothalamus and lowered galanin concentration in thalamus. On the other hand, IND・HCI and IND・HCI on brain VIP.And galanin suppot clearly differences in the molecular mechanisms of the pharmacological effects of the two drugs. Using ^2H-BFM and rat brain synaptosome fraction, specific binding site was detected in thalamus. ^<14>C-IND was found to interact with synaptosome fractions of various rat brain tissue examined. The binding of ^<14>C0IND was inhibited IND・HCI dose-dependently and no substantial differences were observed among the tissues examined. Interestingly, BFM・HCI, propranolol・HCI and imipramine-HCI also exhibited essentially same magnitides of affinity to the IND binding site. These four compounds share a partial structure, of -O-C-C-C-N- or its closely related in common. The significance of this binding site for the pharmacological effects remains to be explored.