Desipramine (hydrochloride)

Desipramine hydrochloride is a first-generation tricyclic antidepressant. Desipramine hydrochloride selectively binds to norepinephrine transporter and blocks neuronal norepinephrine reuptake. Desipramine hydrochloride activates MAPK signaling via ERK1/2, JNK, and p38, represses NF-κB and AP-1 activity, and induces apoptosis via ROS elevation, mitochondrial membrane potential reduction, and intracellular calcium increase. Desipramine hydrochloride also shows anyi-inflammatory activity, inhibiting TNF-α production. Desipramine hydrochloride can be used for the research of hepatocellular cancer, inflammation, and neurological diseases^[1][2][3][4]. In Vitro:Desipramine hydrochloride (3-500 µM; 24 h) reduces the viability of human hepatoma Hep3B cells in a dose-dependent manner^[1].
Desipramine hydrochloride (10-500 µM; 24 h) induces cytotoxicity in human hepatoma Hep3B cells in a dose-dependent manner, as measured by increased LDH release^[1].
Desipramine hydrochloride (3-100 µM; 24 h) increases intracellular ROS production in human hepatoma Hep3B cells in a dose-dependent manner^[1].
Desipramine hydrochloride (3-100 µM µM; 24 h) has its induced cell death in human hepatoma Hep3B cells abolished by the ROS scavenger NAC (HY-B0215) at concentrations up to 30 µM, and partially reduced at 100 µM after 24 h^[1].
Desipramine hydrochloride (3-100 µM; 24 h) reduces mitochondrial membrane potential in human hepatoma Hep3B cells in vitro in a dose-dependent manner^[1].
Desipramine hydrochloride (100 µM; 1-8 h) activates ERK1/2, JNK, and p38 MAPK signaling in human hepatoma Hep3B cells-^[1].
Desipramine hydrochloride (3-100 µM; 24 h) has its induced cell death in human hepatoma Hep3B cells abolished by inhibition of ERK1/2, p38, or JNK MAPK signaling^[1].
Desipramine hydrochloride (30-500 µM) increases intracellular calcium levels in human hepatoma Hep3B cells in a concentration-dependent manner, with increases occurring via both extracellular calcium influx and intracellular calcium release^[1].
Desipramine hydrochloride potently binds to the rat norepinephrine transporter with a K_i of 6.2 nM, showing 25-fold selectivity over the rat serotonin transporter (K_i = 158 nM) ^[3].
Desipramine hydrochloride (1 h) binds to the rat α₂D-adrenoceptor with a K_i of 3.4 μM^[3].
Desipramine hydrochloride potently binds to the human norepinephrine transporter with a K_i of 0.63 nM, has lower affinity for the human serotonin transporter (K_i = 22 nM), and lacks affinity for the human dopamine transporter (K_i >10,000 nM)^[3].
Desipramine hydrochloride (0.01-10 μM; 20 h) dose-dependently inhibits LPS (HY-D1056)-induced TNF-α release from primary human monocytes^[4].
Desipramine hydrochloride (10 μM) reduces TNF-α-induced RANTES release and RANTES mRNA accumulation in A549 human lung epithelial cells^[4].
Desipramine hydrochloride (10 μM) represses TNF-α-induced NF-κB activity in A549 human lung epithelial cells^[4].
Desipramine hydrochloride (10 μM) reduces TPA (HY-18739)-induced AP-1 activity in A549 human lung epithelial cells^[4]. In Vivo:Desipramine (5-20 mg/kg; i.p.; single dose, 30 minutes pre-LPS) hydrochloride dose-dependently inhibits LPS (HY-D1056)-induced serum TNF-α production and increases survival rate to 70% in a murine septic shock model^[4].
Desipramine (10 mg/kg; i.p.; daily; 8 days, 30 minutes pre-Ovalbumin nebulization) hydrochloride reduces lung inflammation by decreasing macrophage and lymphocyte counts in Ovalbumin (HY-W250978)-sensitized rats but does not attenuate bronchial hyperresponsiveness^[4].