Gemazocine is an opioid antagonist. It was first reported in the literature in the 1970’s, and toxicology studies have been performed to characterize its profile.

Volazocine was studied as an analgesic. Information about the current use of this agent is not available.

Oxiramide, an antiarrhythmic agent was studied as a cardiac depressant. However, information about the current use of this compound is not available.

Menabitan is a synthetic cannabinoid exerting analgesic activity.

ADX 10059 is a first-in-class reflux inhibitor that works by reducing activation of the metabotropic glutamate receptor 5 (mGluR5) through negative allosteric modulation (NAM). This approach may lead to a new class of drugs that addresses the causes of GERD rather than just the symptoms. ADX 10059 is a potent selective NAM of the mGluR5, with an IC50 of 17.1 nM on hmGluR5 showing good selectivity compared with > 65 other receptors, transporters, ion channels and enzymes. ADX 10059 completed Phase IIb testing in gastroesophageal reflux disease (GERD) and migraine prevention, demonstrated significant potential in a non-human primate model of Parkinson's disease levodopa induced dyskinesia (PD-LID). However, Addex Pharmaceuticals announced the discontinuation of development of ADX 10059 in December 2009 due to liver enzyme changes.

Gamfexine (WIN 1344) was introduced in the literature in 1966 as an anti-depressant. Although it was reported to be effective in the treatment of withdrawal in schizophrenia, it worsened psychotic symptoms.

Indimilast is dioxodihydropyridopyrimidine derivative patented by global pharmaceutical company AstraZeneca as phosphodiesterase IV inhibitor. Indimilast modulates lung inflammation and causes bronchodilation by increasing intracellular cyclic adenosine 3', 5'-monophosphate in airway smooth muscle and inflammatory cells. Indimilast is potentially useful in chronic obstructive pulmonary disease but its activity was never evaluated in clinical trials.

HU-308 ([(1R,2R,5R)-2-[2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl]-7,7-dimethyl-4-bicyclo[3.1.1]hept-3-enyl]methanol) is a potent, selective agonist for the CB2 receptor. The synthesis and characterization took place in the laboratory of Prof. Mechoulam at the Hebrew University of Jerusalem in the late 1990s. It has analgesic effects, promotes proliferation of neural stem cells,[3] and protects both liver and blood vessel tissues against oxidative stress via inhibition of TNF-α. In vivo, HU-308 has hypotensive, analgesic, and anti-inflammatory activities in mice that can be reversed by the CB2 receptor antagonist SR 144528 but not the CB1 receptor antagonist rimonabant. Pretreatment of mice with HU-308 decreases the I/R-induced tissue damage, inflammatory cell infiltration, tissue, and serum TNF-α, MIP-1, and MIP-2 levels, tissue lipid peroxidation, and apoptosis. HU-308 increases proliferation of HT29 colon cancer cells and growth of tumors in an HT29 mouse xenograft model. The physiological and toxicological properties of this compound have not been evaluated in humans.