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Biochemical evidence for the involvement of central serotonergic neurotransmission in the action of the antidepressant drug Medifoxamine
Author(s) -
Gillon Jeanyves,
Vitte PierreAlain,
Lemonnier Francoise,
Kato Gabor
Publication year - 1994
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430320107
Subject(s) - serotonergic , pharmacology , antidepressant , receptor , chemistry , serotonin , 5 ht receptor , neurotransmission , radioligand , in vivo , mechanism of action , dopaminergic , endocrinology , medicine , in vitro , biology , hippocampus , biochemistry , dopamine , microbiology and biotechnology
Abstract Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5‐HT 1c and 5‐HT 2 receptor subtypes and to 5‐HT uptake sites (IC 50 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5‐HT 2 receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [ 3 H]‐5‐HT uptake and a dose‐dependent down‐regulation of 5‐HT 2 receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5‐HT 2 receptors, which could contribute to its antidepressant effect.