Trimipramine

Trimipramine is a 5-HT receptor antagonist, with pK_i binding values of 6.39, 8.10, 4.66 for 5-HT_1C, 5-HT₂ and 5-HT_1A, respectively. Trimipramine is also a potent and selective inhibitor targeting human noradrenaline (hNAT), serotonin (hSERT) and organic cation transporters (hOCT1, hOCT2) with IC₅₀ values of 4.99 μM, 2.11 μM, 3.72 μM, 8.00 μM, respectively. Trimipramine has vascular activity and anxiolytic efficacy^[1][2][3]. IC50 & Target:pKi: 6.39 (5-HT_1C), 8.10 (5-HT₂), 4.66 (5-HT_1A) IC50: 4.99 μM (hNAT), 2.11 μM (hSERT), 3.72 μM (OCT1), 8.00 μM (hOCT2) In Vitro: Trimipramine displays much higher affinity for 5-HT₂ than for 5-HT_1C receptors^[1].
Trimipramine is a moderate inhibitor of the human NAT and SERT, with the IC₅₀ values of 4.99 μM and 2.11 μM, respectively^[2].
SERT and NAT could represent a target for the antidepressant effects of trimipramine (1 mM, 0.1 mM, 0.01 mM, 1 μM, 0.1 μM; 10 min; HEK293 cells)^[2]. In Vivo: Trimipramine (5 mg/kg/d; 14 d; chronic administration) acts as functions in rats:1. Increasing concentration of regional 5-HT. 5-HT is highest in the frontal cortex and the hippocampus, followed by the olfactory tubercles and the hypothalamus. 2. Decreasing the number of frontal cortex 5-HT₂ and striatal DA D₂ receptors. 3. Increasing in the brain regional level of monoamines and metabolites. thus indicates a greater synthesis rate for dopamine (DA) and 5-HT coinciding with an adaptive down regulation of 5-HT₂ and DA D₂ receptors^[3].