BIOCHEMICAL-EVIDENCE FOR THE INVOLVEMENT OF CENTRAL SEROTONERGIC NEUROTRANSMISSION IN THE ACTION OF THE ANTIDEPRESSANT DRUG MEDIFOXAMINE

Medifoxamine, an antidepressant agent which has an original chemical s tructure, has been shown through in vitro studies, utilising radioliga nd binding in tissue homogenates, to bind with moderately high affinit y to 5-HT1C and 5-HT2 receptor subtypes and to 5-HT uptake sites (IC50 950, 980, and 1,500 nM, respectively). It has been shown to bind in v ivo to rat brain 5-HT2 receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 mu mol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 mu mol/kg), a decrease in the capacity o f [H-3]-5-HT uptake and a dose-dependent down-regulation of 5-HT2 rece ptors in rat cerebral cortex were observed. These results indicate tha t medifoxamine, which has been shown previously to act through dopamin ergic systems, interacts also with central serotonergic neurotransmiss ion and particularly with the 5-HT2 receptors, which could contribute to its antidepressant effect.(C) 1993 Wiley-Liss, Inc.