Vilazodone is a serotonergic antidepressant. The mechanism of the antidepressant effect of vilazodone is not fully understood but is thought to be related to its inhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone’s antidepressant effect are unknown. The side effects include activation of mania/hypomania in patients with bipolar disorder, seizures can occur with treatment in patients with a seizure disorder.

Amitriptyline is a derivative of dibenzocycloheptadiene and a tricyclic antidepressant (TCA) and is mainly used to treat symptoms of depression. It works on the central nervous system (CNS) by inhibiting the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Amitriptyline has been frequently used as an active comparator in clinical trials on newer antidepressants. It is rarely used as a first-line antidepressant nowadays due to its high degree of toxicity in overdose and generally poorer tolerability than the newer antidepressants.

Chlorpheniramine is an antihistamine. Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Chlorpheniramine is used for relieving symptoms of sinus congestion, sinus pressure, runny nose, watery eyes, itching of the nose and throat, and sneezing due to upper respiratory infections (eg, colds), allergies, and hay fever. In addition to being a histamine H1 receptor (HRH1) antagonist, chlorphenamine has been shown to work as a serotonin-norepinephrine reuptake inhibitor or SNRI.

Bicifadine (DOV-220075) is not a narcotic and is well-tolerated and, in preclinical studies, has been shown not to act at any opiate receptor, but inhibits monoamine neurotransmitter uptake by recombinant human transporters in vitro with a relative potency of norepinephrine:serotonin:dopamine of 1:2:17. Bicifadine was in Phase II clinical trial for pain caused by diabetic neuropathy, in addition, was in phase III clinical trial to treat Chronic Low Back Pain, but that studies were discontinued

Lubazodone (YM 992) or (S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride, exhibited the biochemical profile of a selective serotonin (5-HT) reuptake inhibitor (SSRI) with 5-HT2A receptor antagonistic activity. It has been studied in the treatment of depression.

Panuramine, a selective inhibitor of uptake of 5-hydroxytryptamine that was studied as an antidepressant, however, has never been marketed.

Dasotraline, also known as SEP-225,289, is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It has an extended half-life (47-77 hours) that supports the potential for plasma concentrations yielding a continuous therapeutic effect over the 24-hour dosing interval at steady state. Dasotraline has shown a lower potential for abuse than methylphenidate in clinical testing. Dasotraline was discovered by Sunovion Pharmaceuticals Inc. and is currently in development to evaluate its use in treating ADHD in adults and children, and BED in adults in the United States. It has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD, BED or any other disorder.

SKF83959 is a benzodiazepine derivative which acts as an agonist of D1 receptor. Activation of D1 receptors by SKF83959 fails to stimulate adenylyl cyclase and inhibits the stimulation of adenylyl cyclase induced by dopamine but stimulates phosphatidylinositol 4,5-biphosphate hydrolysis in membranes of frontal cortex. SKF83959 was identified as a specific agonist for the heteromer D1/D2 complex. SKF83959 elicit anti-parkinsonism effects in monkeys and rodents. In lower concentrations, SKF83959 inhibits serotonin, norepinephrine and dopamine transporters and is an allosteric regulator of sigma 1 receptor. The compound has demonstrated activity in a preclinical model of depression.

Methoxetamine (abbreviated as MXE) is a novel psychoactive substance that is emerging on the Internet and induces dissociative effects and acute toxicity. MXE acts behaviourally as a typical dissociative anesthetic with stimulant and anxiogenic effects at lower doses, sedative/anesthetic effects at higher doses, and as a disruptor of sensorimotor gating. Its pharmacological effects have not yet been adequately investigated, but recently published articles shown, that MXE differentially affected motor activity, behavior and emotional states in rats, depending on the dose tested. Methoxetamine acts mainly as N-methyl-D-aspartate (NMDA) receptor antagonist and a serotonin reuptake inhibitor.