Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder

* Male and female subjects * Aged 18 to 65 years * Meets Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria for major depressive disorder (MDD) * Current episode has lasted ≥ 8 weeks before Screening * HDRS-17 score ≥ 21 before beginning the washout of all current antidepressant agents and/or adjuvant agents * HDRS-17 score ≥ 21 at Baseline (after 14 days of washout of current antidepressant agents) * Female subjects of childbearing potential with a negative serum pregnancy test prior to entry into the study and who are practicing an adequate method of birth control (eg oral or parenteral contraceptives, intrauterine device, barrier, abstinence) and who do not plan to become pregnant during the course of the study. Female subjects may be included without a negative serum pregnancy test if they are surgically sterile or at least 2 years post-menopausal * Male subjects and their female sexual partner should use an acceptable method of birth control during the study * Clinical laboratory values \< 2 times the upper limit of normal (ULN) or deemed not clinically significant per the investigator and Naurex medical monitor * Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments * Based on both the investigator and Naurex medical monitor's clinical judgment, subjects with eating disorders, obsessive compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), and generalized anxiety disorders secondary to major depressive episodes are permitted

* Axis I diagnosis of delirium, dementia, dysthymia, amnestic or other cognitive disorder, schizophrenia or other psychotic disorder, bipolar I or II disorder, eating disorder (anorexia or bulimia nervosa), obsessive-compulsive disorder, panic disorder, agoraphobia, social phobia, attention-deficit hyperactivity disorder (ADHD), or PTSD * A clinically significant current Axis II diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder * Experiencing hallucinations, delusions, or any psychotic symptomatology in the current episode; lifetime history of psychosis * Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, or a history of seizures or strokes * Currently hospitalized or residing in an in-patient facility during the study participation * Substance abuse within the last 12 months, including greater than or equal to 5 units of alcohol per day where 1 unit = 1/2 pint of beer, 1 glass of wine, or 1 oz. of spirits consumed most weeks or in the opinion of the investigator * Allergy or intolerance to current antidepressant or other current medications * Participation in any clinical trial of an investigational product or device within 30 days of enrollment in this trial * Positive screen for drugs of abuse: cocaine, marijuana, PCP, ketamine, opioid or other agent that in the opinion of the investigator is being abused * Have received electroconvulsive therapy, transcranial magnetic stimulation (TMS), or vagal nerve stimulation (VNS) for the current depressive episode * Post current (past 6 months) suicide risk based on administration of the C-SSRS and the investigator's clinical judgment * Human immunodeficiency virus (HIV) infection (based on the HIV-1 \& HIV-2 antibody screen) or other ongoing infectious disease * Females or female partners of male subjects who are currently pregnant or planning to become pregnant during the course of the study. Women who are breastfeeding * Currently taking prescription (psychiatric treatments, antidepressant treatments) or over-the-counter medications including herbal therapies to treat their MDD or conditions secondary to their period following study drug dosing. Dextromethorphan or tramadol since these are serotonin uptake inhibitors.