Lofepramine

Lofepramine (Lopramine) is a modified tricyclic and orally active antidepressant. Lofepramine inhibits the uptake of Noradrenaline (NA) (HY-13715) and 5-hydroxytryptamine (5-HT) with IC₅₀s of 2.7 μM and 11 μM, respectively. Lofepramine exerts its antidepressant activity by promoting noradrenergic neurotransmission. Lofepramine also enhances serotonergic neurotransmission by inhibiting neuronal uptake of 5-HT and tryptophan pyrrolase. Lofepramine exhibits significant anxiolytic properties. ^[1][2][3][4]. In Vitro:Lofepramine (0.01-100 μM, 10 min) inhibits both ³H-5-HT and ³H-NA uptake into synaptosomal fractions in rats brain cells^[1].
In Vivo:Lofepramine (28-45 mg /kg, i.p., 1 h before experiment) only decreases the uptake of both in rats at 28 mg/kg pretreated with SKF 525A and decreases both 5-HT and Noradrenaline (HY-13715) in intact rats at 45 mg/kg^[1].
Lofepramine (50 mg /kg, i.p., was injected 30 min before intraventricular administration of ³H-5-HT (0.75 _μCi) or ³H-NA (1.2 _μCi)) is effective in inhibiting Noradrenaline (HY-13715) uptake into both fractions (the P2- and S-fractions) ^[1].
Lofepramine (20 mg /kg, i.p., daily, 2 weeks) and it’s desmethylated metabolites, DMI (Desipramine) (HY-B1272A), DML(Desmethyl lofepramine) and DDMI (Desmethyl desipramin), exhibits antidepressant activity in the OB (olfactory bulbectomy) model^[4].