丙咪嗪

IC50: 32 nM (serotonin)

Depression-like behavior is often complicated by chronic pain. Antidepressants including imipramine are widely used to treat chronic pain, but the mechanisms are not fully understood. Imipramine (IC ₅₀ =32 nM) and desipramine (IC ₅₀ =160 nM) are found to be potent inhibitors of the human placental serotonin transporter.

Administration of imipramine reverses social avoidance behavior, significantly increasing the interaction time. 24 days of imipramine treatment in RSD mice significantly decreases stress-induced mRNA levels for IL-6 in brain microglia. Chronic mild stress induces a long-term altered gene expression profile in the prefrontal cortex that is partially reverted by imipramine treatment (10mg/kg, i.p.). Chronic imipramine administration alteres the amino acid dynamics in the brain. In the striatum, the concentrations of asparagine, glutamine and methionine are significantly increased by chronic imipramine administration. In the thalamus and hypothalamus, chronic imipramine administration significantly decreased the valine concentration. Imipramine reduces pain-related negative emotion without influencing pain and that this effect is diminished by denervation of 5-HT neurons and by anti-BDNF treatment. Imipramine also normalizes derangement of ERK/CREB coupling, which leads to induction of BDNF. This suggests a possible interaction between 5-HT and BDNF. Imipramine treatment counteracts the corticosterone administration-induced increase in the reactivity of rat CA3 hippocampal circuitry to the activation of the 5-HT receptor.