STIMULANTS AND ANTIDEPRESSANTS--RELATIONSHIP TO PHARMACOL OGICAL ACITVITY

各种精神治疗药物的识别网站已经被 在中枢神经系统中被识别。在过去的几年里我们 曾尝试确定其他常见精神药物的识别位置 包括三环类抗抑郁药和精神运动兴奋剂在内的药物， 安非他明和哌醋甲酯。在每种情况下都是饱和的，并且 已经描绘了立体特异性结合部位；苯丙胺和 哌甲酸甲酯之间有较好的相关性 一系列类似物的体外亲和力以及至少部分 这些药物的药理特性。最近的研究表明， 下丘脑膜上的(~3H)(+)-苯丙胺结合部位对 循环中的血糖水平。低血糖降低，并且 高血糖增加了(~3H)(+)-苯丙胺结合位点的数量 分别在下丘脑膜中表达。此外，这些变化似乎 要偶联到(Na+K+)(ATPase)的活性；而且有很好的 (~3H)-苯丙胺与(~3H)-哇巴因变化的相关性 在体内和体外均可结合。最近的研究表明， (~3H)-马吲哚是一种化学上无关的厌食剂/精神刺激剂，也可以 用于标记(~3H)(+)-苯丙胺识别位点，并且有 A对(~3H)-马吲哚结合的抑制作用具有良好的相关性 苯乙胺系列及其对大鼠的厌食作用。这些 数据表明，存在一种膜结合的受体复合体，能够 “感应”循环中的葡萄糖浓度和调节两者 糖耐量摄入行为可能与中枢某些方面有关 能量代谢的调节。最近的研究表明， 遗传性肥胖小鼠(ob/ob)在这个系统中存在异常并失败。 对葡萄糖摄食信号作出反应。

Recognition sites for a variety of psychotherapeutic drugs have been identified in the central nervous system. Over the past several years we have attempted to identify recognition sites for other common psychotropic drugs including tricyclic antidepressants and the psychomotor stimulants, amphetamine and methylphenidate. In each case saturable, and stereospecific binding sites have been delineated; and for amphetamine and methylphenidate relatively good correlations have been observed beween the affinities of a series of analogues in vitro and at least some of the pharmacological properties of these agents. Recent work has shown that the (3H) (+)-amphetamine binding site in hypothalamic membranes is sensitive to circulating levels of blood glucose. Hypoglycemia decreases, and hyperglycemia increases, the number of (3H) (+)-amphetamine binding sites in hypothalamic membranes respectively. Furthermore, these changes seemed to be coupled to the activity of (Na+ K+) (ATPase; and there is a good correlation between the changes in (3H) (+)-amphetamine and (3H)-ouabain binding both in vivo and in vitro. More recent studies have shown that (3H)-mazindol a chemically unrelated anorectic/psychostimulant also can be used to label the (3H) (+)-amphetamine recognition site and that there is a good correlation between the inhibition of (3H)-mazindol binding by a series of phenylethylamines and their anorectic potencies in rats. These data suggest the existence of a membrane-bound receptor complex capable of "sensing" circulating glucose concentration and in regulating both glucostatic ingestive behavior and perhaps some aspects of the central regulation of energy metabolism. More recent work has demonstrated that genetically obese mice (ob/ob) have an abnormality in this system and fail to respond to glucoprivic feeding signals.