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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002186-04
Application #
3968527
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code