The present invention relates generally to the enantiomers of para-hydroxy-milnacipran
or congeners thereof. Biological assays revealed that racemic para-hydroxy-milnacipran
is approximately equipotent in inhibiting serotonin and norepinephrine uptake (IC50=28.6
nM for norepinephrine, IC50=21.7 nM for serotonin). Interestingly, (+)-para-hydroxy-milnacipran
is a more potent inhibitor of norepinephrine uptake than serotonin uptake (IC50=10.3
nM for norepinephrine, IC50=22 nM for serotonin). In contrast, (-)-para-hydroxy-milnacipran
is a more potent inhibitor of serotonin uptake compared to norepinephrin uptake
(IC50=88.5 nM for norepinephrine, IC50=40.3 nM for serotonin).
The invention also relates to salts and prodrug forms of the aforementioned compounds.
In certain embodiments, the compounds of the present invention and a pharmaceutically
acceptable excipient are combined to prepare a formulation for administration to
a patient. Finally, the present invention relates to methods of treating mammals
suffering from various afflictions, e.g., depression, chronic pain, or fibromyalgia,
comprising administering to a mammal in need thereof a therapeutically effective
amount of a compound of the present invention.