Rolipram is a selective phosphodiesterase-4 inhibitor discovered and developed by Schering AG as a potential antidepressant drug in the early 1990s. Rolipram was discontinued after clinical trials showed that its therapeutic window was too narrow. Rolipram could not be dosed at high enough levels to be effective without causing significant gastrointestinal side effects. Rolipram promotes apoptosis in HL60 cells through a cAMP-independent mechanism and has been shown to enhance neuronal survival.

Pipamperone (INN, USAN, BAN), also known as Carpiperone and Floropipamide or Fluoropipamide, and as Floropipamide hydrochloride (JAN), is a typical antipsychotic of the butyrophenone family used in the treatment of schizophrenia. It is or has been marketed under brand names including Dipiperon, Dipiperal, Piperonil, Piperonyl, and Propitan. Pipamperone acts as an antagonist of the 5-HT2A, 5-HT2B, 5-HT2C D2, D3, D4, α1-adrenergic, and α2-adrenergic receptors. It shows the much higher affinity for the 5-HT2A and D4 receptors over the D2receptor (15-fold in the case of the D4 receptor, and even higher in the case of the 5-HT2A receptor), is regarded as "highly selective" for the former two sites at low doses. Pipamperone has low and likely insignificant affinity for the H1 and mACh receptors, as well as for other serotonin and dopamine receptors. Low-dose pipamperone (5 mg twice daily) has been found to accelerate and enhance the antidepressant effect of citalopram. Pipamperone is approved in some European countries. At its usually recommended antipsychotic dose (120–360 mg/d), it has relatively weak neuroleptic activity because it is only moderately effective as a dopamine D2-receptor antagonist, even at high doses.

Oxitriptan is an aromatic amino acid with antidepressant activity. In vivo, oxitriptan is converted into 5-hydroxytryptamine (serotonin) as well as other neurotransmitters. Oxitriptan may exert its antidepressant activity via conversion to serotonin or directly by binding to serotonin receptors within the central nervous system. It is used as an antiepileptic and antidepressant. Oxitriptan is a worthwhile addition to the limited treatments available for obsessive-compulsive disorder and panic disorder, two psychiatric disorders which have previously been difficult to manage pharmacologically. Possible gastrointestinal side effects are: nausea, vomiting, abdominal pain, constipation or flatulence, which tend to disappear with continued treatment or, in any case, dose reduction. Other undesirable effects such as anorexia, xerostomia, tachycardia, extrasystoles, dizziness, headache, lightheadedness, tremor or myalgia may occur.

Metergoline is a psychoactive drug of the ergoline chemical class which acts as a ligand for various serotonin and dopamine receptors. Metergoline is an antagonist at various 5-HT receptor subtypes at a relatively low concentration and an agonist at dopamine receptors. Its use has been studied in various clinical settings such as a treatment for seasonal affective disorder, prolactin hormone regulation due to its inhibitory effect on prolactin release premenstrual dysphoric disorder in women and antianxiety treatment

Moclobemide ia an antidepressant that acts on the monoaminergic cerebral neurotransmitter system by reversibly inhibiting monoamine oxidase, primarily type A (RIMA). The metabolism of noradrenaline, dopamine and serotonin is thereby reduced, resulting in increased extracellular concentrations of these neurotransmitters. Increase in the level of serotonin is the most pronounced. Moclobemide administration also leads to increased monoamine receptor stimulation, reversal of reserpine induced behavioral effects, selective depression of the rapid eye movement (REM) sleep, down regulation of beta-adrenoceptors and increases in plasma prolactin and growth hormone levels. It reduces scopolamine-induced performance decrement and alcohol induced performance deficit which suggest a neuroprotective role. Moclobemide is indicated for the treatment of major depressive episodes.

ABP-688 C-11 (8 (3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enoneO-11C-methyl-oxime), a noncompetitive and highly selective antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5). It is a promising PET ligand for the quantification of mGlu5 receptors in humans and animals. It readily crosses the blood-brain barrier. The temporal and spatial changes in mGluR5 availability suggest ABP-688 C-11 PET imaging in epilepsy provide abnormal glutamatergic network during epileptogenesis. ABP-688 C-11 was used in receptors imaging in Major Depressive disorder, chronic neuropathic pain, anxiety and other brain disease investigations.

Saffron is a spice derived from the flower of Crocus sativus, commonly known as the "saffron crocus". Crocin is a water-soluble carotenoid pigment of saffron,that has been used as a spice for flavoring and coloring food preparations, and in Chinese traditional medicine as an anodyne or tranquilizer. Saffron is now used worldwide in folk medicine and is reputed to be useful in treating various human disorders such as heart and blood disorders. Stroke and heart attack are involved in reputed folkloric uses of saffron. Saffron is orally administrated as a decoction. Saffron extract exerts a protective effect on renal ischemia reperfusion induced oxidative damage in rats. Crocin suppresses tumor necrosis factor (TNF) alpha-induced apoptosis of pheochromocytoma (PC12) cells by modulating mRNA expressions of Bcl-2 family proteins, which trigger downstream signals culminating in caspase-3 activation followed by cell death. Depriving cultured PC12 cells of serum/glucose causes a rapid increase in cellular ceramide levels, followed by an increase in the risk of cell death. The accumulation of ceramide was found to depend on the activation of neutral sphingomyelinase (nSMase). Crocin prevented the activation of nSMase by enhancing the transcription of gamma-glutamylcysteinyl synthase, which contributes to a stable glutathione supply that blocks the activity of nSMase.

Vortioxetine is an antidepressant for the treatment of major depressive disorder. Vortioxetine’s mechanism of action is not fully understood. Vortioxetine binds with high affinity to the serotonin transporter and its antidepressant actions are believed to be secondary to enhancing serotonin in the central nervous system through inhibition of reuptake. Vortioxetine also displays binding affinities to other serotonin (5-HT) receptors, including 5-HT3, 5-HT1A, and 5-HT7. Due to multimodal neurotransmitter enhancer profile, it has been suggested that it might need lesser receptor occupancy rate for clinical trials than other selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Since vortioxetine is an agonist and antagonist of multiple serotonin receptors, potential interactions may occur with other medications that alter the serotonergic pathways. There is an increased risk of serotonin syndrome when vortioxetine is used in combination with other serotonergic agents.

Vortioxetine is an antidepressant for the treatment of major depressive disorder. Vortioxetine’s mechanism of action is not fully understood. Vortioxetine binds with high affinity to the serotonin transporter and its antidepressant actions are believed to be secondary to enhancing serotonin in the central nervous system through inhibition of reuptake. Vortioxetine also displays binding affinities to other serotonin (5-HT) receptors, including 5-HT3, 5-HT1A, and 5-HT7. Due to multimodal neurotransmitter enhancer profile, it has been suggested that it might need lesser receptor occupancy rate for clinical trials than other selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Since vortioxetine is an agonist and antagonist of multiple serotonin receptors, potential interactions may occur with other medications that alter the serotonergic pathways. There is an increased risk of serotonin syndrome when vortioxetine is used in combination with other serotonergic agents.

Vortioxetine is an antidepressant for the treatment of major depressive disorder. Vortioxetine’s mechanism of action is not fully understood. Vortioxetine binds with high affinity to the serotonin transporter and its antidepressant actions are believed to be secondary to enhancing serotonin in the central nervous system through inhibition of reuptake. Vortioxetine also displays binding affinities to other serotonin (5-HT) receptors, including 5-HT3, 5-HT1A, and 5-HT7. Due to multimodal neurotransmitter enhancer profile, it has been suggested that it might need lesser receptor occupancy rate for clinical trials than other selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Since vortioxetine is an agonist and antagonist of multiple serotonin receptors, potential interactions may occur with other medications that alter the serotonergic pathways. There is an increased risk of serotonin syndrome when vortioxetine is used in combination with other serotonergic agents.