Alpha methyltryptamine (AMT) is a tryptamine (indole ethylamine) derivative, which was developed in the 1960's by Upjohn with the intention for use as an antidepressant. It was used in Russia under the trade name Indopan for the treatment of Bipolar disorder and some form of depression, but currently not being produced because of serious side effects. In the 1990's, alpha-methyltryptamine became regulated as a Schedule I controlled substance in the United States. Pharmacologically, AMT has high affinity for the serotonin (5-HT) transporter, a number of 5-HT receptors, and potently inhibits reuptake of monoamines dopamine, 5-HT, and norepinephrine reuptake. AMT is also a monoamine oxidase A inhibitor that conceivably could contribute to its pharmacological effect and this drug also the most potent inhibitor of semicarbazide-sensitive amine oxidase (SSAO).

O-Desmethyl tramadol (O-Desmethyltramadol, O-DSMT) is a metabolite of tramadol. O-Desmethyltramadol is an opioid analgesic and the main active metabolite of tramadol. (+)-O-Desmethyltramadol is the most important metabolite of tramadol produced in the liver after tramadol is consumed. This metabolite is considerably more potent as a μ-opioid agonist than the parent compound. O-desmethyl tramadol, inhibits 5-hydroxytryptamine type 2C receptors expressed in xenopus oocytes. O-desmethyl tramadol inhibits functions of M(1) receptors but has little effect on those of M(3) receptors. O-desmethyl tramadol has been widely used clinically and has analgesic activity.

Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant properties as well as for their abuse potential. Mephedrone is a stimulant of dopamine (DA) release and blocks its reuptake through its interaction with the dopamine transporter. Furthermore, it has some affinity for various 5-hydroxytryptamine (5-HT) receptor subtypes. Neurotoxic effect of mephedrone on 5-HT and DA systems remains controversial. Although some studies in animal models reported no damage to DA nerve endings in the striatum and no significant changes in brain monoamine levels, some others suggested a rapid reduction in 5-HT and DA transporter function. Persistent serotonergic deficits were observed after binge like treatment in a warm environment and in both serotonergic and dopaminergic nerve endings at high ambient temperature. Oxidative stress cytotoxicity and an increase in frontal cortex lipid peroxidation were also reported. Despite the re-classification of mephedrone as a Class B restricted substance by the United Kingdom and restrictive legislation by the United States, international policy regarding mephedrone control is still developing and interest in synthetic amphetamine-like drugs could drive the development of future mephedrone analogues.

Parafluorofentanyl is a selective mu-opioid agonist, an analog of fentanyl, developed by Janssen. The drug was not developed for human use but is produced and abused illegally.

Mirfentanil was developed as CNS analgesic with a short duration of action. It induced antinociception predominately through mu opioid receptors. It was shown that at doses larger than those, which exert opioid effects, mirfentanil had nonopioid analgesic effects. The drug was successfully encapsulated in liposomes having a variety of compositions. The lipid composition of the formulation was varied to optimize the stabilization of liposomes and the encapsulation of solutes. Mirfentanil participated in phase II clinical trials for the treatment of pain. However, this study was discontinued.

Trefentanil is a short-acting synthetic opioid of the piperidine class. The drug caused potent analgesia with the peak effect occurring 3 min after injection. There was no significant difference in analgesic potency of trefentanil and alfentanil as measured by tolerance to tibial pressure at 3 min. Trefentanil had a pharmacokinetic and pharmacodynamic profile similar to alfentanil, with a small extent of tissue distribution and a rapid blood/brain equilibration. Trefentanil caused significant respiratory depression at doses of 32 ug/kg and 64 ug/kg. It is a mu-opioid receptor agonist. Trefentanil produced naloxone reversible anti-nociception equi-efficacious to that of fentanyl.

Norbolethone is a 19-nor anabolic steroid first synthesized in 1966. During the 1960s it was administered to humans in efficacy studies concerned with short stature and underweight conditions. It has never been reported by doping control laboratories prior to 2001. Norbolethone matches the description for what is described as a "designer steroid. " In fact, Norbolethone was given in clinical trials over 30 years ago and never given the green light. No supply was ever manufactured, and no test was ever developed to detect this substance, yet ironically, it was suspected of being used in the 2000 Olympics based on blood and urine assays done by the IOC. Norbolethone was used in the treatment of idiopathic underweight, prevention of indomethacin-induced intestinal ulcers.