IDENTIFICATION AND PHARMACODYNAMICS OF LIPOPHILIC LIGAND

一种对中心具有高亲和力的亲脂物质 苯二氮卓类受体已从大鼠脑组织中提取出来。 这种亲脂物质可降低γ-氨基丁酸的刺激作用 突触神经体对氯的摄取。在初步研究中 苯二氮卓类拮抗剂氟马西平阻断了这种抑制作用 亲脂性物质对γ-氨基丁酸的影响 刺激氯离子摄取。亲脂性物质不会 看起来像是苯二氮卓类、β-卡洛林或多肽。 这笔赠款的目的应该有助于解释为什么人类会不同。 对苯二氮卓类药物的反应。第一个具体目标是 获得纯度为95%至100%的亲脂物质。国家的现状 将使用ART光谱设备来确定结构 亲脂性物质。亲脂性的亲和力 中枢和外周苯二氮卓类受体的物质将 通过其取代-H-氟马西平和-H-PK11195的能力进行评估 分别为特异性结合。亲脂性的选择性 苯二氮卓类受体的物质将通过其 用来取代放射性配体的特定结合的能力 对其他受体的选择性。亲油性的力量 复方降低蝇毒酚刺激的大鼠对氯离子的摄取 将对突触神经体进行测量。控制应激反应 氯离子转运的改变，一个习惯于处理的组将 被包括在这些后面的研究中。这是一种机制 亲脂性物质启动蝇毒酚刺激的减少 氯的吸收将被澄清。氟马西平、PK11195和Ro15- 将对4513人进行检查，以了解其对抗减产的能力 在蝇毒酚刺激的由亲脂性引起的氯摄取中 实质性的。

A lipophilic substance with high affinity for central benzodiazepine receptors has been extracted from rat brain tissue. The lipophilic substance reduces gamma-aminobutyric acid-stimulated uptake of chloride in synaptoneurosomes. In preliminary studies the benzodiazepine antagonist, flumazepil, blocked the inhibitory effect of the lipophilic substance on gamma-aminobutyric acid- stimulated chloride uptake. The lipophilic substance does not appear to be a benzodiazepine, a beta-carboline or a polypeptide. The objectives of this grant should help explain why humans vary in response to the benzodiazepines. The first specific aim is to obtain the lipophilic substance in 95 to 100 purity. State of the art spectroscopic equipment will be used to determine the structure of the lipophilic substance. The affinity of the lipophilic substance for central and peripheral benzodiazepine receptors will be assessed by its ability to displace -H-flumazepil and -H-PK11195 specific binding, respectively. The selectivity of the lipophilic substance for benzodiazepine receptors will be determined by its ability to displace the specific binding of radio-ligands with selectivity for other receptors. The potency of the lipophilic compound in decreasing muscimol-stimulated chloride uptake in synaptoneurosomes will be measured. To control for stress induced alterations of chloride transport, a handled-habituated group will be included in these latter studies. The mechanism by which the lipophilic substance initiates the decrease in muscimol-stimulated chloride uptake will be clarified. Flumazepil, PK11195 and Ro15- 4513 will be examined for an ability to antagonize the reduction in muscimol-stimulated chloride uptake elicited by the lipophilic substance.