Dexoxadrol is a sigma receptor agonist. Dexoxadrol, the D-isomer of dioxodrol, which produces PCP-like behavioural effects and displaces bound [3H]PCP, was a potent blocker of the PCP-sensitive, voltage-gated K+ channel. Dexoxadrol was developed as analgesics for use in humans, however, severe side effects including psychotomimetic effects, unpleasant dreams and aberrations stopped the clinical evaluation of dexoxadrol. Dexoxadrol is a NMDA receptor antagonist, which possesses high affinity to the phencyclidine binding site within the NMDA receptor associated ion channel.

RAC BHFF is the potent and selective GABAB receptor positive allosteric modulator that increases the potency and efficacy of GABA. Exhibits anxiolytic and anticonvulsant activity in vivo and is orally active. RAC BHFF reduces alcohol’s reinforcing properties in alcohol-preferring rats and adds further support to the hypothesis that the positive allosteric modulators of the GABAB receptor may constitute a novel class of agents with therapeutic potential for alcohol dependence.

GW7647 is a potent and highly selective PPARα agonist (EC50 values are 6, 1100 and 6200 nM for human PPARα, PPARγ and PPARδ receptors respectively). GW7647 has being shown to protect the heart from ischemia/reperfusion injury in mouse model. GW7647 attenuated ischemia/reperfusion-induced release of multiple proinflammatory cytokines and inhibited neutrophil accumulation and myocardial expression of matrix metalloproteinases-9 and -2. Furthermore, GW7647 inhibited nuclear factor-kappaB activation in the heart, accompanied by enhanced levels of inhibitor-kappaBalpha.

is a potent, selective, brain penetrant, orally active serotonin 5-HT(6) receptor antagonist with cognitive enhancing, anxiolytic and antidepressant properties. It is able to regulate sleep and wakefulness in rodents. In addition it demostrates antinociceptive and antiepileptic potentials.

(-)-∆8-Tetrahydrocannabinol (∆8-THC) has a very similar pharmacologic profile as (-)-∆9-tetrahydrocannabinol (∆9-THC), the most active constituent of cannabis. Delta-8-tetrahydrocannabinol (THC) has activity in man similar to that of its double-bond isomer, delta-9-THC. The spatial orientation of the side chain seems to play a pivotal role in cannabinergic activity. Introduction of a triple bond in the benzylic position of the n-heptyl-D8-THC analogue led to the classical cannabinoid AMG-1 with high CB1 and moderate CB2 affinity. AMG-1 is an analgesic drug which is a cannabinoid agonist.

Sazetidine-A (6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol or AMOP-H-OH) is a "silent desensitizer" of neuronal nicotinic acetylcholine receptors (nAChRs), meaning that it desensitizes the receptor without first activating it. Later it was shown that Sazetidine-A is an agonist of native and recombinant alpha4beta2 nAChRs but shows differential efficacy on alpha4beta2 nAChRs subtypes. In animal models it is able to regulate the gain in body weight, alcohol and nicotine dependence. Sazetidine-A exerts analgesic, antidepressant and anxiolytic properties.

BCTC is an orally effective mixed TRPV1/TRPM8 antagonist. Inhibits acid- and capsaicin-induced activation of rat TRPV1 receptors (IC50 values are 6.0 and 35 nM respectively). BCTC is shown to have robust antihyperalgesic properties in rat models of inflammatory and neuropathic pain. TRPM8 specific antagonist BCTC demonstrated excellent anti-tumor activity in PCa DU145 cells, and therefore has the potential to become a targeted therapeutic strategy against PCa.

DB09173 (Butyrfentanyl or butyrylfentanyl) is a potent, short-acting mu opioid receptor agonist, and an analog of fentanyl, differing by only one methyl group. It has no approved medical indications but is being used for recreational purposes, with cases of fatal overdoses reported in Europe and the United States. Pre-clinical studies of butyrfentanyl are scarce; however, the few available studies suggest that butyrfentanyl is about 30 times less potent than fentanyl itself, and has significant antinociceptive properties, as demonstrated by the acetic acid writhing test in rodents. DB09173 is being abused for its opioid effects. As with other mu-opioid agonists, it can induce respiratory depression which may lead to death and numerous deaths have been reported. No studies of butyrfentanyl dependence or cross-dependence conducted in humans could be identified.

Cinobufagin is a bufadienolide compound extracted from the dried venom secreted by the parotid glands of toads and one of the glycosides in the traditional Chinese medicine ChanSu, with potential antineoplastic activity. Cinobufagin has been shown to have clinical applications in cancer treatment as well as immunomodulatory and analgesic properties. Cinobufagin induces apoptosis of osteosarcoma cells through inactivation of Notch signaling. Cinobufagin induces autophagy-mediated cell death in human osteosarcoma U2OS cells through the ROS/JNK/p38 signaling pathway. Cinobufagin significantly relieved cancer pain in mice and raised their pain threshold, mainly upregulating the expression levels of beta-Endorphin and μ- opioid receptor in the hind paw tumor and adjacent tissue. In combination with gemcitabine-oxaliplatin cinobufagin was used in clinical trial for the treatment of locally advanced or metastatic gallbladder carcinoma.

Norketamine is one of the major metabolites of Ketamine, which is routinely used as an anesthetic. Norketamine is a potent antagonist of the N-methyl-D-aspartate receptor and is believed to contribute to the analgesic effects of ketamine. In animal models, norketamine has been noted to increase the glomerular filtration rate by remodeling the cellular cytoskeleton, and it has been identified as having possible antidepressant effects.