Desomorphine is the common name for 4,5--epoxy-17- methylmorphinan-3-ol or dihydrodesoxymorphine-D. It is an opioid analogue and morphine derivative in which the 6-hydroxyl group and the double bond at carbons 7 and 8 of morphine are reduced. Desomorphine can cross the blood–brain barrier, binding to opioid receptors, similar to the pharmacokinetic distribution of all phenanthrene-structured alkaloids. Taking Desomorphine causes euphoria as well as sedative and analgesic relief. In addition to its faster onset than other powerful painkillers drugs such as morphine, desomorphine also initiates less sedative effects and seems to have favorable postoperative results, such as reduced need for catheterization, less dizziness, and decreased vomiting incidence. In comparison with Morphine, Desomorphine is faster reduced. It follows that it has to be taken it more frequently to get the same effects. Furthermore, it causes side effects such as respiratory and gastrointestinal problems and increased blood pressure. In addition, Desomorphine’s withdrawal symptoms are up to three times longer than Morphine’s. This leads to the conclusion that Desomorphine is more addictive. At present, desomorphine is classified as a narcotic drug (DEA code number 9055) in Schedule I of the U.S. Controlled Substances Act and is listed as a controlled substance under the international Single Convention on Narcotic Drugs of 1961.

Emicerfont (GW876008) is a nonpeptide vcorticotropin-releasing factor type 1 (CRF1) receptor antagonist. It was in clinical trials for the treatment of anxiety disorders, irritable bowel syndrome and major depressive disorder however development of emicerfont has been discontinued.

Vestipitant, also known as GW597599, is a neurokinin1 receptor antagonist that was being developed by GlaxoSmithKline for the treatment of postoperative nausea and vomiting. Vestipitant is one of the most potent and selective NK(1) receptor antagonists ever discovered, showing appropriate pharmacokinetic properties and in vivo activity. Its actions support the utility of NK(1) receptor blockade in the alleviation of anxiety and, possibly, depression. It was under development as a potential antiemetic and anxiolytic drug, and as a treatment for tinnitus and insomnia. Vestipitant was shown to improve sleep maintenance in patients with primary insomnia, with no associated next-day cognitive impairment. The effects on wake after sleep onset and total sleep time were maintained following repeated dosing. Vestipitant has anxiolytic properties and a good safety profile. Vestipitant was investigated for potential effect against chronic tinnitus as a stand-alone treatment and in conjunction with a selective serotonin reuptake inhibitor, paroxetine. Although well-tolerated vestipitant, alone or in combination with paroxetine, was not effective in ameliorating tinnitus in this patient group.

Etonitazene is a potent and selective mu-opioid agonist. It was developed in CIBA. Administration of etonitazene may induce respiratory depression, and therefor etonitazene is not used in humans. Etonitazene is explicitly listed as an illegal drug under UN convention and is illegal throughout the world.

Etrabamine is a potent agonist of dopamine D2 receptors. It was being studied in the treatment of Parkinson's disease, however, its development has been discontinued.

Fenobam is a selective and potent metabotropic glutamate (mGlu)5 receptor antagonist with inverse agonist activity. Fenobam was previously investigated as an anxiolytic in a number of phase II studies in the early 1980s. These studies revealed a mixed picture of anxiolytic efficacy, with double blind, placebo controlled trials variously reporting the compound as active or inactive. This discrepancy was not easily reconciled based on patient numbers, dose level, duration of treatment, or outcome measures. The positive effects seen in animal models of fragile X syndrome (FXS) treated with fenobam or other mGluR5 antagonists, the apparent lack of clinically significant adverse effects, and the potential beneficial clinical effects seen in this pilot trial support further study of the compound in adults with FXS.

Amedalin (UK-3540) is a selective norepinephrine reuptake inhibitor developed in the 1970s. Amedalin was a potential antidepressant compound. It has no significant effect on reuptake of serotonin and dopamine and no antihistamine or anticholinergic properties. This drug was never marketed.

Difenamizole is a non-steroidal anti-inflammatory drug and analgesic of the pyrazolone group related to metamizole. Mice given difenamizole per os showed maximal anti-nociceptive activity 30--60 min after administration. Difenamizole may depress the release of catecholamines from monoaminergic neurons. The analgesic action of difenamizole was antagonized by intracerebral injection of dopamine but not by norepinephrine. An analgesic action of difenamizole may be related to the dopaminergic system and difenamizole may depress the release of dopamine in the striatum, therefore, difenamizole may demonstrate an analgesic action following depression of dopaminergic neuronal activity in the striatum and preventing the binding of dopamine with the receptors.

Dichlormezanone is the skeletal muscle relaxant. This metathiazanone was found to have a mephenesin-like type of action characterized by paralyzing, anticonvulsant, and hypothermic activities. Dichlormezanone produced an ascending type of paralysis, associated with a marked ataxia. It has anti-electroshock and anti-chemoshock activities. It was found to be active after oral administration and to have a prolonged duration of action. The daily administration of sublethal doses of dichlormezanone to albino rats for 5 consecutive days produced only an initial loss of weight. No significant hematologic alteration or macroscopic lesion of any of the viscera, attributable to medication with either drug, was observed.

ORG-28611 (SCH-900,111) is a potent cannabinoid receptor full agonist, developed by Organon International for treatment pain. In preclinical studies, Org 28611 exhibited high affinity for both CB1 and CB2 cannabinoid receptors, as determined by radioligand competition binding assays and rapidly metabolized by mouse and human hepatic microsomes and showed higher total levels in the brain compared to plasma. In clinical trials, Org 28611 does not provide enough sedation for outpatient surgical procedures, does not induce anterograde amnesia and causes undesirable subjective effects at higher doses. However, bolus doses up to 3 μ/kg (with maximum initial plasma concentrations of 24 ng/mL) or mean plasma levels up to 4 ng/mL are well tolerated and make it worthwhile to further explore the analgesic or antiemetic properties.