Propylnorapomorphine is a potent and selective D2 receptor agonist. Propylnorapomorphine is used as a tool compound to label dopamine receptors in rodent brain, and elicits dopaminergic behavioural effects. It stimulates motor activity, induces stereotypic behaviour and sexual stimulation. Propylnorapomorphine was investigated in clinical trial against Parkinson's disease and schizophrenia

The investigational psychopharmacologic drug candidate CP 615003 (NGD 91-3) is a potent subtype-selective partial agonist at the GABA-A receptor complex. It was designed to be fast acting without causing the sedation, memory impairment, addiction or potentiation of effects of alcohol associated with conventional anti-anxiety medication. Tissue distribution studies conducted during early clinical development of CP 615003 suggested limited brain penetration. In the Phase II clinical study, subjects tested at the high dose of NGD 91-3 showed a trend toward efficacy that did not achieve statistical significance.

Mitragynine is the main active alkaloid constituent of the plant Mitragyna speciosa Korth. Mitragyna speciosa Korth. (M. speciosa), from the Rubiaceae family, is a tropical medicinal plant native to Southeast Asia. In Malaysia, M. speciosa leaves are known as Ketum or Biak, and in Thailand as Kratom. M. speciosa has been historically used in Southeast Asia as a stimulant drug and in its traditional context as a remedy for various symptoms. Pharmacological activities are mainly mediated via opioid receptors as well as neuronal Ca2+ channels, expression of cAMP and CREB protein and via descending monoaminergic system. Mitragynine acted as a partial agonist at mu-opioid receptors, in contrast, at kappa-opioid receptors, mitragynine was a competitive antagonist, similarly, mitragynine acted as an antagonist at delta-mu-opioid receptors, but with very low potency. Experimental studies in animals have now shown that mitragynine has an addictive potential, however, only at higher doses. Human users in countries of frequent use with a traditional context report a rather low daily consumption with only mild side effects. Kratom and mitragynine can be instrumentalized to enhance physical work power and endurance. A major reason for Kratom consumption is its reported efficacy to replace opiates in chronic users. This makes the Kratom plant preparation and also the isolated compound mitragynine interesting options to treat opiate addiction. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule 1 controlled substances.

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.