JZL184 is an irreversible inhibitor for monoacylglycerol lipase (MAGL), the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG). Selectivity of JZL 184 over other serine hydrolases makes it useful compound to study endogenous 2-AG signaling. Administration of JZL184 to mice was reported to cause dramatic elevation of brain 2-AG leading to several cannabinoid-related behavioral effects. JZL184 was found effective in preclinical models of anxiety and chemotherapy-induced neuropathic pain.

Selfotel is a competitive NMDA antagonist with (-)-enantiomer is more active than ( )-enantiomer. Selfotel was investigated in phase III clinical trials for ischemic stroke and severe head injury. Development of the drug was discontinued due to lack of efficacy and possible neurotoxicity discovered in clinical trials.

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.

Genipin is an aglycone derived from an iridoid glycoside called Geniposide (structure on the bottom) present in fruit of Gardenia jasmindides Ellis. Genipin have been demonstrated to have diverse pharmacological activities including anti-inflammatory, antioxidative, neuroprotective, and neurotrophic effects. Genipin is an excellent natural cross-linker for protein, collagen, gelatin, and chitosan cross-linking and can be considered as a substitute for glutaraldehyde. Due to cross-linking properties genipin can be used in controlling drug delivery. In addition genipin exerts choleretic action.

A-317491 (ABT-202) is a non-nucleotide antagonist of P2X3 and P2X2/3 receptor activation. A-317491 potently blocked recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and was highly selective (IC50 >10 uM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes. A-317491 also blocked native P2X3 and P2X2/3 receptors in rat dorsal root ganglion neurons. Blockade of P2X3 containing channels was stereospecific because the R-enantiomer (A-317344) of A-317491 was significantly less active at P2X3 and P2X2/3 receptors. A-317491 dose-dependently (ED50 = 30 umolkg s.c.) reduced complete Freund's adjuvant-induced thermal hyperalgesia in the rat. Studies indicate that the P2X3 receptor is implicated in both neuropathic and inflammatory pain. P2X3 receptor is a promising target for therapeutic intervention in cancer patients for pain management. ABT-202 had been in phase I clinical trials by Abbott and NeuroSearch for the treatment of pain. However, this research has been discontinued.

Gelsemine is the principal alkaloid in Gelsemium sempervirens Ait. A single intrathecal injection of gelsemine produced potent and specific antinociception in formalin-induced tonic pain, bone cancer-induced mechanical allodynia, and spinal nerve ligation-induced painful neuropathy. Gelsemine exhibits potent and specific antinociception in chronic pain by acting at spinal α3 glycine receptors. Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine.

Neriifolin is a cardenolide glycoside that is digitoxigenin in which the hydroxy goup at position 3 has been converted to its 6-deoxy-3-O-methyl-alpha-L-glucopyranoside derivative. Found in the seeds of Cerbera odollamand in Thevetia ahouia and Thevitia neriifolia. Neriifolin reduced viability of cancer cells, induced S and G2/M phase arrests of the cell cycle, and stimulated apoptosis.

L-fucose is a hexose deoxy sugar found on N-linked glycans on mammalian, insect and plant cell surfaces. Deficiency in L-fucose has been observed in several pathological conditions including cancer and atherosclerosis. On the other hand, L-fucose is an inhibitor of the sodium/myo-inositol transporter which may play a roll in the development of diabetes. L-fucose is has been considered as a diagnostic biomarker in several forms fo cancer.

GBR-12935 (1-{2-benzhydryloxyethyl}-4-(3-phenylpropyl)piperazine) is a potent and selective inhibitor of dopamine transporter. Gist-Brocades originally initiated studies of GBR-12935 for the treatment of cocaine dependence. Tritium-labeled GBR-12935 may be used in radioligand binding studies. GBR-12935 is considered to be the metabolite of vanoxerine, another piperazine dopamine uptake inhibitor.

Beta-erythroidine is an organic heterotetracyclic indole alkaloid isolated from the seeds and other parts of Erythrina species. A drug used to produce muscle relaxation (excepting neuromuscular blocking agents). Its primary clinical and therapeutic use is the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. Also used for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in multiple sclerosis. Beta-erythroidine is a neuronal nicotinic acetylcholine receptor antagonist. The beta-erythroidine and its more potent derivative (2,7-dihydro) have been used as muscular relaxants in numerous clinical applications. This activity is attributed to a antagonistic action of the dihydro-beta-erythroidine with the nicotinic receptors of acetyl choline.