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(S)-Duloxetine is a potent inhibitor of serotonin and norepinephrine reuptake (Kis = 4.6 and 15.6 nM, respectively, for rat synaptosomes).1 It also inhibits dopamine reuptake (Ki = 369 nM). (S)-Duloxetine suppresses spontaneous firing activity in vivo in the dorsal raphe and locus coeruleus (ED50s = 99 and 475 µg/kg, respectively).2 It also decreases immobility time and increases latency to first immobility in the forced swim test in mice when administered at doses of 16 and 32 mg/kg.3 Formulations containing (S)-duloxetine have been used in the treatment of major depressive disorder, generalized anxiety disorder, chronic neuropathic and musculoskeletal pain, and fibromyalgia.
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1. LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology 8(1), 23-33 (1993).
2. Blockade of the serotonin and norepinephrine uptake processes by duloxetine: In vitro and in vivo studies in the rat brain. J. Pharmacol. Exp. Ther. 277(1), 278-286 (1996).
3. Use of latency to immobility improves detection of antidepressant-