BRAIN RECOGNITION SITES FOR STIMULANTS AND ANTIDEPRESSANTS

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。这些结合位点中有几个， 包括苯二氮类药物、阿片类药物和各种神经镇静剂 后来被证明是真正的药理受体，因为 药物与其各自的识别部位的结合是必要的(和许多 次数足够)对药物作用的要求。在过去几年里 我们已经尝试为其他常见的 精神药物，包括三环类抗抑郁药和精神运动 兴奋剂，安非他明和哌醋甲酯。在每种情况下，都是可饱和的 已经描绘了立体特异性结合部位；苯丙胺和 观察到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。三环类抗抑郁药， 包括丙咪嗪和地昔帕明，也与不同的识别有关 在功能和结构上与 5-羟色胺和去甲肾上腺素的突触前摄取部位。 因此，放射性标记的抗抑郁剂是研究抑郁症的有用探针。 中枢和外周神经递质摄取的机制 组织，并在各种临床条件下。最近的研究表明 下丘脑膜上的(~3H)(+)-苯丙胺结合部位为 对循环中的血糖水平敏感。低血糖降低， 和高血糖增加，(~3H)(+)-苯丙胺结合的数量 分别位于下丘脑膜。此外，这些变化 似乎与(Na+K+)(ATPase)的活性相偶联； (~3H)(+)-苯丙胺的变化与 (~3H)-哇巴因在体内和体外的结合。最近的研究表明 研究表明，化学上不相关的厌食剂/精神刺激剂(~3H)-马吲哚， 也可用于标记[~3H](+)-苯丙胺识别位点 ~(3 H)-马吲哚结合的抑制作用与二者之间存在良好的相关性 通过一系列苯乙胺及其对大鼠的厌食能力。

Recognition sites for a variety of psychotherapeutic drugs have been identified in the central nervous system. Several of these binding sites, including those for benzodiazepines, opiates, and various neuroleptics have subsequently been shown to be true pharmacological receptors in that the binding of drug to its respective recognition site is a necessary (and many times sufficient) requirement for drug action. 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. Tricyclic antidepressants, including imipramine and desipramine, also bind to distinct recognition sites that are functionally and structurally associated with the presynaptic uptake sites for serotonin and norepinephrine respectively. Thus, radiolabeled antidepressants have been useful probes in studying the mechanisms of neurotransmitter uptake in both central and peripheral tissues, and under a variety of clinical conditions. 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.