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.

Norcodeine is the N-demethylated derivative of codeine. It has relatively little opioid activity in its own right, but is formed as a metabolite of codeine following ingestion. Codeine and its other major metabolites codeine-6-glucuronide and norcodeine have weak affinity to opioid μ-receptors.

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.

Pfizer was developing PF-4455242, a selective, short-acting (non-"inactivating") antagonist of the κ-opioid receptor. PF-4455242 was pursued in phase I clinical trial for the treatment of the bipolar disorder and was also investigated as a treatment for depression and substance abuse. In September 2010 Pfizer discontinued the development of the compound.

Asimadoline is an orally active, highly selective kappa-opioid receptor agonist with approximately 500-fold greater affinity for human kappa-, as compared with either delta- or mu-opioid receptors. Due to its high selectivity for the kappa-opioid receptor, asimadoline does not produce mu-opioid like side effects. It is investigated for use/treatment in irritable bowel syndrome, pruritus, postoperative ileus. A drug interaction study investigating the coadministration of asimadoline with ketoconazole was performed in healthy volunteers - a two to three-fold increase in AUC and Cmax of asimadoline was observed with concomitant administration of ketoconazole. The most common adverse events are diarrhea, nausea, sinusitis, headache and fatigue.

Norcodeine is the N-demethylated derivative of codeine. It has relatively little opioid activity in its own right, but is formed as a metabolite of codeine following ingestion. Codeine and its other major metabolites codeine-6-glucuronide and norcodeine have weak affinity to opioid μ-receptors.

Dextrorphan is an active metabolite of dextromethorphan, is an antitussive agent, which was found in cough medicines. Dextrorphan is a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, sigma 1 receptor agonist, so as is an agonist of mu and kappa opioid receptors. In addition was found, that dextrorphan possessed anticonvulsive and neuroprotective effects.

AH-7921 (3,4-Dichloro-N-([1-(dimethylamino)cyclohexyl] methyl)benzamide) is an N-substituted cyclohexylmethylbenzamide classified as an opioid analgesic with high addictive liability. The compound acts as an agonist of μ-opioid receptors, although at high doses it can also stimulate κ-opioid receptors. In animal studies, AH-7921 produced typical morphine-like actions, i.e., antinociception, respiratory depression, sedation, miosis, inhibition of gut propulsion, and lowered body temperature, with a potency almost equipotent to that of morphine. There is limited information available on the routes of administration and the doses of AH-7921 used. The compound is taken orally, nasally, by smoking, and, less commonly, by intravenous injection. Minimal oral effective doses for complete pain suppression by AH 7921 are 1.25 and 13.8 mg/kg for canine and rhesus monkey, respectively.