Mechanism of action +Binding profile Receptor Ki (nM) SERT 0.7~0.8 NET 7.5 DAT 240 5-HT2A 504 5-HT2C 916 5-HT6 419<unk>  inhibits the reuptake of serotonin and norepinephrine (NE) in the central nervous system.<unk>  increases dopamine (DA) specifically in the prefrontal cortex, where there are few DA reuptake pumps, via the inhibition of NE reuptake pumps (NET), which is believed to mediate reuptake of DA and NE.<unk>  has no significant affinity for dopaminergic, cholinergic, histaminergic, opioid, glutamate, and GABA reuptake transporters, however, and can therefore be considered to be a selective reuptake inhibitor at the 5-HT and NE transporters.<unk>  undergoes extensive metabolism, but the major circulating metabolites do not contribute significantly to the pharmacologic activity. In vitro binding studies using synaptosomal preparations isolated from rat cerebral cortex indicated that<unk>  was approximately 3 fold more potent at inhibiting serotonin uptake than norepinephrine uptake. Major depressive disorder is believed to be due in part to an increase in pro-inflammatory cytokines within the central nervous system. Antidepressants including ones with a similar mechanism of action as<unk> , i.e. serotonin metabolism inhibition, cause a decrease in proinflammatory cytokine activity and an increase in anti-inflammatory cytokines; this mechanism may apply to<unk>  in its effect on depression but research on cytokines specific to<unk>  therapy is lacking. The analgesic properties of<unk>  in the treatment of diabetic neuropathy and central pain syndromes such as fibromyalgia are believed to be due to sodium ion channel blockade. Pharmacokinetics Absorption:<unk>  is acid labile, and is formulated with enteric coating to prevent degradation in the stomach.<unk>  has good oral bioavailability, averaging 50% after one 60 mg dose. There is an average 2-hour lag until absorption begins with maximum plasma concentrations occurring about 6 hours post dose. Food does not affect the Cmax of<unk> , but delays the time to reach peak concentration from 6 to 10 hours. Distribution:<unk>  is highly bound (>90%) to proteins in human plasma, binding primarily to albumin and α1-acid glycoprotein. Volume of distribution is 1640L. Metabolism:<unk>  undergoes predominately hepatic metabolism via two cytochrome P450 isozymes, CYP2D6 and CYP1A2. Circulating metabolites are pharmacologically inactive.<unk>  is a moderate CYP2D6 inhibitor. Elimination: Administered in healthy young male subjects at doses between 20–40 mg twice a day, had a half-life of 12.5 hours and its pharmacokinetics are dose proportional over the therapeutic range. Steady-state is usually achieved after 3 days. Only trace amounts (<1%) of unchanged<unk>  are present in the urine and most of the dose (approx. 70%) appears in the urine as metabolites of<unk>  with about 20% excreted in the feces. Smoking is associated with a decrease in<unk>  concentration.
Duloxetine
Atomoxetine
Dapoxetine
Fluoxetine
Edivoxetine
Vortioxetine
Guanfacine
Nabilone