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.
