Drugs that possess norepinephrine reuptake inhibition, either selectively or in combination with serotonin reuptake inhibition, have been approved for multiple indications including major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), and pain disorders such as diabetic neuropathy and fibromyalgia. Venlafaxine was the first dual norepinephrine / serotonin reuptake inhibitor to be approved for the treatment of MDD and is widely prescribed because of its rapid onset of action and superior efficacy. In an effort to develop novel norepinephrine reuptake inhibitors for evaluation in a variety of predictive animal models, the venlafaxine-like scaffold was reinvestigated. Our efforts in this area lead to the identification of a potent and highly selective norepinephrine reuptake inhibitor. Details about the identification of this compound from data mining, in vitro screening analyses, structure-activity relationships, and pharmacokinetic parameters will be presented as well as data for multiple in vivo models.