Trimipramine displays much higher affinity for 5-HT ₂ than for 5-HT _1C receptors.

The chronic administration of Trimipramine (5 mg/kg/day), as delivered by the osmotic minipump in 14 days produce significant increases in the regional concentration of 5-HT. The increases are highest in the frontal cortex and the hippocampus, followed by the olfactory tubercles and the hypothalamus. The Trimipramine treatment also produces marked increases in brain 5-HIAA concentrations ranging from 63% in the hippocampus to 25% in the nucleus accumbens with intermediate values for the hypothalamus, olfactory tubercles, frontal cortex and nucleus accumbens. Trimipramine treatment produces significant increases in DA concentrations in the nucleus accumbens, striaturn, and olfactory tubercles reaching 43, 21 and 11% respectively. Chronic administration of Trimipramine produces a marked reduction in the number of frontal cortex 5-HT ₂ and striatal DA D ₂ receptors. The chronic administration of Trimipramine produces an increase in the brain regional level of monoamines and metabolites indicating a greater synthesis rate for DA and 5-HT coinciding with an adaptive down regulation of 5-HT ₂ and DA D ₂ receptors.