Differential binding of /sup 3/H-imipramine and /sup 3/H-mianserin in rat cerebral cortex

Journal Article · Sun Nov 15 23:00:00 EST 1981 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(81)90661-5· OSTI ID:5801965

Dumbrille-Ross, A; Tang, S W; Coscina, D V

Drug competition profiles, effect of raphe lesion, and sodium dependency of the binding of two antidepressant drugs /sup 3/H-imipramine and /sup 3/H-mianserin to rat cerebral cortex homogenate were compared to examine whether the drugs bound to a common ''antidepressant receptor.'' Of the neurotransmitters tested, only serotonin displaced binding of both /sup 3/H-imipramine and /sup 3/H-mianserin. /sup 3/H-Mianserin binding was potently displaced by serotonin S/sub 2/ antagonists and exhibited a profile similar to that of /sup 3/H-spiperone binding. In the presence of the serotonin S/sub 2/ antagonist spiperone, antihistamines (H/sub 1/) potently displaced /sup 3/H-mianserin binding. /sup 3/H-Imipramine binding was displaced potently by serotonin uptake inhibitors. The order of potency of serotonergic drugs in displacing /sup 3/H-imipramine binding was not similar to their order in displacing /sup 3/H-spiperone or -3H-serotonin binding. Prior midbrain raphe lesions greatly decreased the binding of /sup 3/H-imipramine but did not alter binding of /sup 3/H-mianserin. Binding of /sup 3/H-imipramine but not /sup 3/H-mianserin was sodium dependent. These results show that /sup 3/H-imipramine and /sup 3/H-mianserin bind to different receptors. /sup 3/H-Imipramine binds to a presynaptic serotonin receptor which is probably related to a serotonin uptake recognition site, the binding of which is sodium dependent. /sup 3/H-Mianserin binds to postsynaptic receptors, possibly both serotonin S/sub 2/ and histamine H/sub 1/ receptors, the binding of which is sodium independent.

• Research Organization: Clarke Institute of Psychiatry, Toronto, Canada
• OSTI ID: 5801965
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 29:20; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METALS
AMINES
ANIMALS
ANTIDEPRESSANTS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BIOLOGICAL LOCALIZATION
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CEREBRAL CORTEX
CEREBRUM
DATA
DRUGS
ELEMENTS
EXPERIMENTAL DATA
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
INFORMATION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METALS
NERVOUS SYSTEM
NEUROREGULATORS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PSYCHOTROPIC DRUGS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
RECEPTORS
RESPONSE MODIFYING FACTORS
RODENTS
SEROTONIN
SODIUM
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
UPTAKE
VERTEBRATES