STIMULANTS AND ANTIDEPRESSANTS--RELATIONSHIP TO PHARMACOLOGICAL ACTIVITY

各种精神治疗药物的识别网站有 在中枢神经系统中被发现。在过去的时间里 几年来，我们一直试图确定识别地点 其他常见精神药物，包括三环类 抗抑郁药和精神运动兴奋剂苯丙胺 和哌醋酸甲酯。在每一种情况下，都是饱和的，并且是立体特定的 已经划定了结合部位；安非他明和 观察到了相对较好的相关性。 一系列类似物在体外和体外的亲和力之间 至少这些药剂的一些药理特性。 最近的研究表明，(~3H)(+)-苯丙胺结合位点 在下丘脑膜中对循环中的 血糖。低血糖下降，高血糖 增加，(~3H)(+)-苯丙胺结合位点的数量增加 分别为下丘脑膜。此外，这些 这些变化似乎与(Na+K+)的活性有关 (ATPase；并且在这些变化之间有很好的相关性 (~3H)-(+)-苯丙胺和(~3H)-哇巴因在体内和 在试管中。最近的研究表明，(~3H)-马吲哚a 也可以使用化学上无关的厌食剂/精神刺激剂 标记(~3H)(+)-苯丙胺认知位点，并且有一个 黄曲霉毒素对(3)-马吲哚结合的抑制作用 一系列苯乙胺及其对大鼠的厌食紧张性。 这些数据表明膜结合受体的存在。 能够“感应”循环中葡萄糖浓度的复合体 在调节血糖素摄取行为方面，也许 能量代谢的中枢调节的某些方面。 最近的研究表明，遗传性肥胖的小鼠 (ob/ob)本系统异常且未响应 普罗普利克进食信号。在过去的一年里，我们 发展了一种测量欧拜因敏感的~(86)Rb摄取的方法 转化为突触神经体，并使用这种方法测量 厌食药物治疗后的“钠泵”活动 在遗传性肥胖的啮齿动物身上。

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 between 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)- ovabain 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 cognition site and that there is a good correlation between the inhibition of (3)-mazindol binding by a series of phenylethylamines and their anorectic otencies 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. Recent work has demonstrated that genetically obese mice (ob/ob) have an abnormality in this system and fail to respond to glucoprivic feeding signals. Over the past year, we have developed a method for measuring oubain-sensitive 86Rb uptake into synaptoneurosomes and have used this method to measure "sodium pump" activity after treatment with anorectic drugs and in genetically obese rodents.