A neuropeptide with diverse biological activities
Milnacipran-d5 is intended for use as an internal standard for the quantification of milnacipran by GC- or LC-MS. Milnacipran is an orally bioavailable serotonin and norepinephrine reuptake inhibitor (SNRI).1 It selectively inhibits the human serotonin transporter and norepinephrine transporter over the dopamine transporter (IC50s = 420, 77, and 6,100 nM, respectively). It also selectively inhibits sodium-dependent serotonin and norepinephrine uptake over dopamine uptake in rat cerebral cortical synaptosomes (IC50s = 28.0, 29.6, and >10,000 nM, respectively).2 Milnacipran is an antagonist of the serotonin (5-HT) receptor subtype 5-HT3A as well as nicotinic acetylcholine receptors (nAChRs; IC50s = 63.5 and 14.3 μM, respectively) but does not inhibit other 5-HT, adrenergic, dopamine, muscarinic acetylcholine, histamine, NMDA, sigma, opioid, or GABA receptors (Kis = >10,000 nM).2,3 In vivo, milnacipran (30 mg/kg) increases withdrawal threshold and latency in response to tactile and heat stimulation, respectively, in nerve-ligated mice.4 Formulations containing milnacipran have been used in the treatment of fibromyalgia pain.
1.Chen, C., Dyck, B., Fleck, B.A., et al.Studies on the SAR and pharmacophore of milnacipran derivatives as monoamine transporter inhibitorsBioorg. Med. Chem.18(4)1346-1349(2008) 2.Mochizuki, D., Tsujita, R., Yamada, S., et al.Neurochemical and behavioural characterization of milnacipran, a serotonin and noradrenaline reuptake inhibitor in ratsPsychopharmacology (Berl)162(3)323-332(2002) 3.Ueta, K., Suzuki, T., Uchida, I., et al.In vitro inhibition of recombinant ligand-gated ion channels by high concentrations of milnacipranPsychopharmacology (Berl)175(2)241-246(2004) 4.Suzuki, T., Ueta, K., Tamagaki, S., et al.Antiallodynic and antihyperalgesic effect of milnacipran in mice with spinal nerve ligationAnesth. Analg.106(4)1309-1315(2008)
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