Biochemical evidence for the involvement of central serotonergic neurotransmission in the action of the antidepressant drug Medifoxamine

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-HTqc and 5-HT2 receptor subtypes and to 5-HT uptake sites (I& 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT2 receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 pmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 pmollkg), a decrease in the capacity of l3H1-5-HT uptake and a dose-dependent down-regulation of 5-HT2 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-HT2 receptors, which could contribute to its antidepressant effect.