3-(4-chlorophenyl)-1-(1-methyl-3-oxo-2-phenyl-5-propan-2-ylpyrazol-4-yl)urea (Cpd43) is a low MW compound synthesized as an agonist for FPR2 and has been shown to have this function in human leukocytes. In vivo, Cpd43 exerts anti-inflammatory effects in murine ear inflammation and air-pouch models, which require FPR2 has agonistic activities for human FPR1 and FPR2/ALX. The EC50 values of Cpd43 for FPR1 and FPR2/ALX were 65 nM and 22 nM, respectively, in the aequorin assay that measured calcium mobilization. Cpd43 exerted significant anti-inflammatory effects on a severe experimental model of RA, in which endogenous AnxA1, the natural ligand for FPR2, also exerted inhibitory effects. In addition, Cpd43 reduced RANKL-mediated osteoclastogenesis and inhibited the production of IL-6 by macrophages, as well the activation of human RA FLS, through effects that appeared to be dependent on interaction with FPR2. These findings suggest that therapeutic agonists of FPR may have important beneficial actions on inflammation and bone loss in RA.

SKF-83822 is a D1/D5 receptor agonist, which activates D1-like receptors coupled to stimulation of adenyl cyclase (AC), but not phosphoinositide (PI) hydrolysis. SKF-83822 is used as a tool compound to study the role of AC-coupled D1 receptors.

Methyl-1-testosterone(M1T)(17alpha-hydroxy-17-methyl- 5-androst-1-en-3-one) is a new designer steroid that is most likely produced to circumvent the legal restrictions. It is advertised to be highly anabolic and moderately androgenic and not convertible to estrogens. However, in scientific literature, it was reported to show anabolic properties of 25% and androgenic properties of 50% compared with testosterone propionate after im injection in castrated rats. In February 2006, Health Canada (Federal Department) warned consumers not to use M1T-containing products because of potentially serious health risks such as liver disorders and hardening of the arteries. Since 2006, M1T is explicitly listed on the World Anti-Doping Agency list of prohibited substances, and therefore, its use by athletes is prohibited.

INT-777 is a semisynthetic bile acid that acts as an agonist of a transmembrane G protein-coupled receptor, TGR5. The novel roles of TGR5 in different diseases make it become a new drug target. It was shown, that INT-777 stimulated insulin secretion in pancreatic β-cells, reduced inflammation and inhibited atherosclerosis in mice.

Sunifiram (DM235) is a piperazine derived research chemical which has anti-amnesiac effects in animal studies. Though Sunifiram is a piracetam derivative, it has a different chemical structure from the racetams and is chemically classed as a piperazine alkaloid. It is known to work in two ways, both as an ampakine that stimulates the activity of glutamine receptors and as a cholinergic that increases the production and release of acetylcholine. Like many nootropics, Sunifiram’s precise mechanisms of action are not entirely understood. However, it is believed that its primary action is that of an ampakine, which means that after crossing the blood-brain barrier it binds to AMPA-type glutamate receptors in the brain. This stimulates the production of glutamate, a vital neurotransmitter that plays the pivotal role in neural activation. Sunifiram is also thought to act as a cholinergic, increasing the production and release of the neurotransmitter acetylcholine. Though the exact process by which this occurs has not been identified, an Italian animal study showed that tests using piperazine compounds such as Sunifiram had a cholinergic effect similar to that of piracetam. No serious side effects of Sunifiram have been documented, but it’s important to remember that no human studies or clinical trials have been conducted.

8-Epiprostaglandin E1 (8-iso-PGE1) arises by isomerization of PGE1. This isoprostane found in human semen. 8-iso-PGE1 has very low biological activity relative to PGE1. Intravenous administration of 8-iso-PGE1 decreased systemic arterial pressure slightly and increased heart rate and myocardial contractile force slightly. The magnitude of the systemic hypotensive effect of 8-iso-PGEl was equivalent to approximately 1/125 to 1/250 of that of PGE1 in dogs. On the other hand, the pulmonary hypertensive action of 8-iso-PGE1 was 5 times greater than that of PGE1. 8-iso-PGE1 is an agonist of prostanoid TP receptor. It was proposed as a prostaglandin D2 receptor antagonist for use in the treatment of androgenic alopecia.

BRL-54443 is a 5-HT1E and 5-HT1F receptor agonist with pKi of 8.7 and 9.25, respectively, with a weak binding affinity for 5-HT1A, 5-HT1B, 5-HT1D receptors. BRL-54443 (3-300 ug/paw) significantly reduced formalin-induced flinching in rats, indicating that it could be used as a therapeutic strategy to reduce inflammatory pain..

15-deoxy-Δ12,14-Prostaglandin J2 (15d-PGJ2) is a cyclopentanone prostaglandin and the agonist of endogenous PPAR gamma ligand, that is formed via the elimination of two molecules of water of prostaglandin D2. 15d-PGJ2 possesses anti-inflammatory effects. Experiments with animal models revealed, that 15d-PGJ2 may represent a potential therapeutic strategy in rheumatoid arthritis. Besides, 15d-PGJ2, given either systemically or locally in mice can control ongoing asthma pathological abnormalities, including eosinophil and neutrophil infiltration, mucus exacerbation, and lung remodeling triggered by ovalbumin. It was suggested, that potential exists to exploit 15d-PGJ2 as a therapeutic agent in asthma. It is known, the determination of individual prostaglandins, including 15d-PGJ2 in urine samples could improve the understanding of particular prostaglandins species under various physiological and pathological conditions. Recently was suggested the sensitive method for determination of 15d-PGJ2 and its application in human plasma samples of patients with diabetes.

AM-1241, was developed at the University of Connecticut. AM-1241 was derived from the known non-selective indole class of cannabinoid receptor agonists represented by WIN55212-2 and JWH-015. Compared to earlier agonists that exhibited modest selectivities, AM-1241 exhibited 82-fold selectivity for CB2 over CB1 based on binding affinity assays. Using AM-1241, it was demonstrated that a selective CB2 receptor agonist provides relief of pain without the psychotropic effects produced by a pan-cannabinoid receptor agonist. After injection of AM-1241 into the hindpaw of a mouse, analgesic activity toward a thermal stimulus applied to the same paw was observed. Co-administration of a CB2 receptor antagonist blocked the effect, while a CB1 antagonist did not. The results of this initial study led researchers to investigate the use of a CB2 receptor selective agonist for the treatment of pain as well as other disease states that involve the CB2 receptor. It was found that AM-1241 inhibited nociception in CB+/+ mice, but not CB2+/+ littermates, providing strong evidence of its direct activation of CB2. AM-1241 was shown to dose-dependently inhibit capsaicin-induced release of the pain biomarker calcitonin gene-related peptide (CGRP) in rat spinal cord slices, a result that also suggests the presence of CB2 in neurons of the spinal cord. AM-1241 has being shown to be a promising target for the management of cancer pain.