Anorectic activities of serotonin uptake inhibitors: correlation with their potencies at inhibiting serotonin uptake in vivo and /sup 3/H-mazindol binding in vitro

Journal Article · Thu Dec 31 23:00:00 EST 1987 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(88)90135-X· OSTI ID:6412360

Angel, I; Taranger, M A; Claustre, Y; Scatton, B; Langer, S Z

The mechanism of anorectic action of several serotonin uptake inhibitors was investigated by comparing their anorectic potencies with several biochemical and pharmacological properties and in reference to the novel compound SL 81.0385. The anorectic effect of the potent serotonin uptake inhibitor SL 81.0385 was potentiated by pretreatment with 5-hydroxytryptophan and blocked by the serotonin receptor antagonist metergoline. A good correlation was obtained between the ED/sub 50/ values of anorectic action and the ED/sub 50/ values of serotonin uptake inhibition in vivo (but not in vitro) for several specific serotonin uptake inhibitors. Most of the drugs tested displaced (/sup 3/H)-mazindol from its binding to the anorectic recognition site in the hypothalamus, except the pro-drug zimelidine which was inactive. Excluding zimelidine, a good correlation was obtained between the affinities of these drugs for (/sup 3/H)-mazindol binding and their anorectic action indicating that their anorectic activity may be associated with an effect mediated through this site. Taken together these results suggest that the anorectic action of serotonin uptake inhibitors is directly associated to their ability to inhibit serotonin uptake and thus increasing the synaptic levels of serotonin. The interactions of these drugs with the anorectic recognition site labelled with (/sup 3/H)-mazindol is discussed in connection with the serotonergic regulation of carbohydrate intake.

• Research Organization: Laboratoires d'Etudes, Paris (France)
• OSTI ID: 6412360
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 43:8; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
CENTRAL NERVOUS SYSTEM AGENTS
CORRELATIONS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
IN VIVO
INDOLES
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
SEROTONIN
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
UPTAKE