Chelidonic acid (CA) is a γ-pyrone which is contained in the rhizome of Chelidonium majus L. It has multiple pharmacological effects including those of a mild analgesic, an antimicrobial, an oncostatic, a central nervous system sedative and the anti-inflammatory effect. Chelidonic acid evokes antidepressant-like effect through the up-regulation of BDNF in forced swimming test. Chelidonic acid administration significantly increased the mRNA expression of hippocampal estrogen receptor-β. The levels of hippocampal interleukin (IL)-1β, IL-6, and tumor necrosis factor-α were effectively attenuated by the administration of chelidonic acid. In addition, chelidonic acid significantly increased the levels of 5-hydroxytryptamine (serotonin), dopamine, and norepinephrine compared with those levels for the mice that were administered distilled water in the hippocampus. Chelidonic acid might serve as a new therapeutic strategy for the regulation of depression associated with inflammation.

Methyl jasmonate (MJ) is a natural cyclopentanone lipid belonging to the jasmonates (JAs) family of plant oxylipin stress hormones (oxygenated fatty acids). Methyl jasmonate is found universally in the plant kingdom and functions to regulate plant growth and development, as well as in stress responses through signal transduction pathways. Methyl jasmonate has recently been found to have anti-cancer activity. MJ (1) arrests cell cycle, inhibiting cell growth and proliferation, (2) causes cell death through the intrinsic/extrinsic proapoptotic, p53-independent apoptotic, and nonapoptotic (necrosis) pathways, (3) detaches hexokinase from the voltage-dependent anion channel, dissociating glycolytic and mitochondrial functions, decreasing the mitochondrial membrane potential, favoring cytochrome c release and ATP depletion, activating pro-apoptotic, and inactivating antiapoptotic proteins, (4) induces reactive oxygen species mediated responses, (5) stimulates MAPK-stress signaling and redifferentiation in leukemia cells, (6) inhibits overexpressed proinflammatory enzymes in cancer cells such as aldo-keto reductase 1 and 5-lipoxygenase, and (7) inhibits cell migration and shows antiangiogenic and antimetastatic activities. Finally, MJ may act as a chemosensitizer to some chemotherapics helping to overcome drug resistant. The complete lack of toxicity to normal cells and the rapidity by which MJ causes damage to cancer cells turn MJ into a promising anticancer agent that can be used alone or in combination with other agents. Methyl jasmonate detached hexokinase 2 from a voltage-dependent anion channel causing a reduction in mitochondrial transmembrane potential that led to the release of cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis. Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered oxidative phosphorylation and led to cell necrosis. Methyl jasmonate may be an adjuvant therapy for liver tumors due to its mechanism in cancer cells compared to that in normal cells: The major function is to inhibit glycolysis instead of changing aerobic metabolism.

Du-24565 is a potent and selective inhibitor of the synaptosomal uptake of serotonin. At higher concentration, it affects the uptake of norepinephrine and dopamine. It is a potential antidepressant and can be useful as a pharmacological tool to study the role of 5-HT in the central nervous system. DU-24565 had little effect on serotonin or tyrosine accumulation in human melanoma cells but suppressed the uptake of extracellular Dopa. In vitro, DU-24565 inhibited the proliferation of PC-3, DU-145 and LNCaP human prostate carcinoma cells in a dose-dependent manner.

Erucamide is a fatty acid amide, which is similar to the classical endocannabinoid analog oleoylethanolamide. It was discovered in mice, that erucamide may regulate the central nervous system and may have the potential to antagonize depression and anxiety and these effects of the compound may be related to the regulation of the hypothalamus-pituitary-adrenal axis (HPA).

β-phenylethylamine (2-phenylethylamine) is a small amine containing alkaloid synonymous with phenethylamine and the acronym PEA; in the human body it has a neuromodulator/neurotransmitter role and is known as a trace amine due to its low quantity relative to other bioactive amino acids. PEA was characterized as a substrate for type B monoamine oxidase. PEA functions by activating trace amine receptors (including TAAR1 and TAAR2) thereby regulating monoamine turnover. Ring-substituted phenethylamines, commonly known as 2Cs, are designer drugs that are emerging as new drugs of abuse. PEA administration may be therapeutic in selected depressed patients.

Menthone is a naturally occurring organic compound. It is found in oils of peppermint, Japanese mint, pennyroyal, Micromeria abyssinica benth, geranium and other oils. It is widely used as fragrances and flavors in the cosmetic, perfume, drug, and food industries. Menthone is a naturally occurring pesticide. Menthone and isomenthone were mild skin irritants and of low acute dermal toxicity in rabbits. Neither showed any sensitizing potential in volunteer studies with dilute solutions. In rats, menthone demonstrated a moderate to low acute oral toxicity. On repeated oral administration, menthone produced increases in liver, kidney and spleen weights of rats. Mutagenic activity was reported for menthone in the bacterium Salmonella typhimurium (Ames test) and in fruitflies.

Selective, potent, orally bioavailable full 5-HT1A antagonist. S-(+)-enantiomer of (±)-LY426965 is more active in comparison with its opposite enantiomer (R)-(-)-LY 426965. LY426965 completely reversed the effects of nicotine withdrawal on the auditory startle reflex in rats. In microdialysis experiments, LY426965, when administered with fluoxetine, significantly increased extracellular levels of serotonin above those achievable with fluoxetine alone. In electrophysiological studies, the administration of LY426965 both blocked and reversed the effects of fluoxetine on 5-HT neuronal activity. Preclinical results indicate that LY426965 may have clinical use as a pharmacotherapy for smoking cessation and depression and related disorders.

L-760735 is a non-peptide substance P receptor (Neurokinin 1 (NK1) receptor) antagonist. It exerts anxiolytic, antidepressant and antinociceptive actions in animals. Merck was developing an L- 760735 as a potential antidepressant.

WAY-181187 is a high affinity and selective 5-HT6 agonist. It displays 60-fold selectivity over other 5-HT and monoamine receptors. WAY-181187 stimulates cAMP, ERK1/2 and Fyn kinase signaling pathway through serotonin receptor activation. WAY-181187 produced both antidepressant-like and anxiolytic-like effects in the animal model. It had been in phase I clinical trial for the treatment of anxiety disorders but this research has been discontinued.

LY-450108 had been in phase I clinical trial by Lilly, where was shown, that this drug safe and well tolerated in healthy subjects. This drug in the preclinical studies on animal models for the treatment of depression and Parkinson's disease.