Milnacipran

Milnacipran is an orally active Serotonin (HY-B1473A) and Norepinephrine (HY-13715) reuptake inhibitor. Milnacipran inhibits monoamine transporters, especially the norepinephrine transporter and the serotonin transporter (K_i values of 31 and 8.5 nM, respectively). Milnacipran inhibits pERK1/2 activation. Milnacipran has antidepressant, anxiolytic and analgesic properties. Milnacipran inhibits biting behavior in mice. Milnacipran can be used in the study of major depressive disorder, anxiety disorders, and neuropathic pain (e.g., fibromyalgia)^{[1][2][3][4][5][6][7][8]}. In Vitro:Milnacipran shows high affinity for 5-HT and NA transporters (K_i = 8.5 and 31 nM, respectively)^[2].
Milnacipran (10-100 µM; 3 min) reduces the amplitude of NMDA (HY-17551)-induced currents in rat spinal lamina II neurons^[5].
Milnacipran (100 µM; 10 min) suppresses NMDA (HY-17551)-induced pERK1/2 activation in superficial dorsal horn neurons^[5].
In Vivo:Milnacipran (30-60 mg/kg; p.o.; single dose) shows anxiolytic effects in rats^[2].
Milnacipran (30-120 mg/kg; p.o.) increases withdrawal threshold to tactile stimulation and latency to heat stimulation in a dose-dependent manner in rats with spinal nerve ligation (SNL)^[4].
Milnacipran (0.01-0.1 µmol; intrathecal) suppresses hyperalgesia in a dose-dependent manner in mice with intrathecal NMDA-induced thermal hyperalgesia^[5].
Milnacipran (3-30 mg/kg; i.p.) suppresses impulsive, aggressive, and depressive-like behaviors in male C57BL/6N mice^[6].
Milnacipran (20-60 mg/kg; i.p.) suppresses food intake in fasted male C57BL/6J and A^y mice, increases hypothalamic POMC and CART mRNA levels, and does not elevate plasma corticosterone or blood glucose^[7].
Milnacipran (0.1-10 μg/site; intrathecal) inhibits Serotonin-induced biting behavior in male ICR mice^[8].