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; add 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)-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 cognition 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. Recent work has demonstrated that genetically obese mice (ob/ob) nave an abnormality in this system and fail respond to glucoprivic feeding signals. Over the past year, we have developed a method for measuring ouabain-sensitive uptake into synaptoneurosomes and have used this method to measure """"""""sodium pump"""""""" activity after treatment with anorectic drugs and in genetically obese rodents.
