Dihydromorphine is a semi-synthetic opioid structurally related to and derived from morphine. The 7,8-double bond in morphine is reduced to a single bond to get dihydromorphine. Dihydromorphine is a moderately strong analgesic and is used clinically in the treatment of pain and also is an active metabolite of the analgesic opioid drug dihydrocodeine. Dihydromorphine occurs in trace quantities in assays of opium on occasion, as does dihydrocodeine, dihydrothebaine, tetrahydrothebaine, etc. The process for manufacturing dihydromorphine from morphine for pharmaceutical use was developed in Germany in the late 19th century, with the synthesis being published in 1900 and the drug introduced clinically as Paramorfan shortly thereafter. A high-yield synthesis from tetrahydrothebaine was later developed.
Dextromoramide is a powerful opioid analgesic approximately three times more potent than morphine but shorter acting. It is subject to drug prohibition regimes, both internationally through UN treaties and by the criminal law of individual nations, and is usually prescribed only in the Netherlands.
Methorphan comes in two isomeric forms, each with differing pharmacology and effects:
Lefetamine (Santenol) is a drug which is a stimulant and also an analgesic with effects comparable to codeine.
Metopon is an opioid analogue that is a methylated derivative of hydromorphone which was invented in 1929 as an analgesic.
Hydroxypethidine (Bemidone) is an opioid analgesic that is an analogue of the more commonly used pethidine (meperidine). Hydroxypethidine is slightly more potent than meperidine as an analgesic, 1.5x meperidine in potency, and it also has NMDA antagonist properties like its close relative ketobemidone.
Tapentadol, brand names Nucynta among others, is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs within 32 minutes of oral administration, and lasts for 4–6 hours.
Metazocine is an opioid analgesic related to pentazocine. While metazocine has significant analgesic effects, mediated through a mixed agonist–antagonist action at the mu opioid receptor, its clinical use is limited by dysphoric and hallucinogenic effects which are most likely caused by activity at kappa opioid receptors and/or sigma receptors.
Prodine is an opioid analgesic that is an analog of pethidine (meperidine). It was developed in Germany in the late 1940s.
Trimeperidine (Promedol) is an opioid analgesic that is an analogue of prodine. It was developed in the early 1950s in the USSR during research into the related drug pethidine.
Phenazocine is an opioid analgesic drug, which is related to pentazocine and has a similar profile of effects.
Propiram is a partial μ-opioid receptor agonist and weak μ antagonist analgesic from the ampromide family of drugs related to other drugs such as phenampromide and diampromide. It was invented in 1963 in the United Kingdom by Bayer but was not widely marketed, although it saw some limited clinical use, especially in dentistry. Propiram reached Phase III clinical trials in the United States and Canada.
Dimepheptanol, also known as methadol or racemethadol, is a synthetic opioid analgesic related to methadone. It has similar effects to other opioids, including analgesia, sedation and euphoria, as well as side effects like itching, nausea and respiratory depression.
Acetylmethadol, also known as methadyl acetate, is a synthetic opioid analgesic. It is a racemic mixture of alphacetylmethadol (α-acetylmethadol) and betacetylmethadol (β-acetylmethadol), which are in turn racemic mixtures of levacetylmethadol and D-α-acetylmethadol and L-β-acetylmethadol and D-β-acetylmethadol, respectively. Hence, acetylmethadol has four possible optical isomers. All of these isomers have been shown to partially or fully substitute for the discriminative stimulus effects of heroin in rats, and thus it can be inferred that, in addition to LAAM which is used clinically as such, they are all likely to be active opioid analgesics in humans.
Alphamethadol (INN), or α-methadol, also known as alfametadol, is a synthetic opioid analgesic. It is an isomer of dimepheptanol (methadol), the other being betamethadol (β-methadol). Alphamethadol is composed of two isomers itself, L-α-methadol, and D-α-methadol. The former compound, L-α-methadol, is an important active metabolite of levacetylmethadol (LAAM), an opioid substitute drug that is used clinically. Both of alphamethadol's isomers bind to and activate the μ-opioid receptor and are active as opioid analgesics, similarly to those of alphacetylmethadol (α-acetylmethadol).
Betamethadol (INN), or β-methadol, also known as betametadol, is a synthetic opioid analgesic. It is an isomer of dimepheptanol (methadol), the other being alphamethadol (α-methadol). Betamethadol is composed of two isomers itself, L-β-methadol, and D-β-methadol. Based on structure-activity relationships it can be inferred that both isomers are likely to be active as opioid analgesics, similarly to those of betacetylmethadol (β-acetylmethadol).
Myrophine (Myristylbenzylmorphine) is an opiate analogue that was developed in 1952. It is a derivative of morphine.
Normorphine is an opiate analogue, the N-demethylated derivative of morphine, that was first described in the 1950s when a large group of N-substituted morphine analogues were characterized for activity. The compound has relatively little opioid activity in its own right, but is a useful intermediate which can be used to produce both opioid antagonists such as nalorphine, and also potent opioid agonists such as N-phenethylnormorphine. with its formation from morphine catalyzed by the liver enzymes CYP3A4 and CYP2C8.
Isomethadone (INN, BAN; trade name Liden; also known as isoamidone) is a synthetic opioid analgesic and antitussive related to methadone that was used formerly as a pharmaceutical drug but is now no longer marketed. Isomethadone was used as both an analgesic and antitussive. It binds to and activates both the μ- and δ-opioid receptors, with the (S)-isomer being the more potent of the two enantiomers. Isomethadone is a Schedule II controlled substance in the United States, with an ACSCN of 9226 and a 2014 aggregate manufacturing quota of 5 g. The salts in use are the hydrobromide (HBr, free base conversion ratio 0.793), hydrochloride (HCl, 0.894), and HCl monohydrate (0.850). Isomethadone is also regulated internationally as a Schedule I controlled substance under the United Nations Single Convention on Narcotic Drugs of 1961.
Alphacetylmethadol (INN), or α-acetylmethadol (AAM), is a synthetic opioid analgesic. Its levorotary enantiomer, levacetylmethadol, is an FDA-approved treatment for opioid addiction; however as of 2003 it is no longer used in the United States for this purpose. Alphacetylmethadol is very similar in structure to methadone, a widely prescribed treatment for opioid addiction. In the United States, it is a Schedule I controlled substance under the Controlled Substances Act, with an ACSCN of 9603 and a 2013 annual manufacturing quota of 2 grammes.
