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.
Lefetamine (Santenol) is a drug which is a stimulant and also an analgesic with effects comparable to codeine.
Thebacon, or dihydrocodeinone enol acetate, is a semisynthetic opioid that is similar to hydrocodone and is most commonly synthesised from thebaine. Thebacon was invented in Germany in 1924, four years after the first synthesis of hydrocodone. Thebacon is a derivative of acetyldihydrocodeine, where only the 6–7 double bond is saturated. Thebacon is marketed as its hydrochloride salt under the trade name Acedicon, and as its bitartrate under Diacodin and other trade names. The hydrochloride salt has a free base conversion ratio of 0.846. Other salts used in research and other settings include thebacon's phosphate, hydrobromide, citrate, hydroiodide, and sulfate.
Nicomorphine is the 3,6-dinicotinate ester of morphine. It is a strong opioid agonist analgesic two to three times as potent as morphine with a side effect profile similar to that of dihydromorphine, morphine, and diamorphine.
Nicocodeine is an opioid analgesic and cough suppressant, an ester of codeine closely related to dihydrocodeine and the codeine analogue of nicomorphine. It is not commonly used in most countries, but has activity similar to other opiates. Nicocodeine and nicomorphine were synthesized in 1904, and introduced in 1957 by Lannacher Heilmittel of Austria. Nicocodeine is metabolised in the liver by demethylation to produce nicomorphine, also known as 6-nicotinoylmorphine, and subsequently further metabolised to morphine. Side effects are similar to those of other opiates and include itching, nausea and respiratory depression. Related opioid analogues such as nicomorphine and nicodicodeine were first synthesized. The definitive synthesis, which involves treating anhydrous codeine base with nicotinic anhydride at 130 °C, was published by Pongratz and Zirm in Monatshefte für Chemie in 1957, simultaneously with the two analogues in an article about amides and esters of various organic acids.
Metopon is an opioid analogue that is a methylated derivative of hydromorphone which was invented in 1929 as an analgesic.
Phenadoxone is an opioid analgesic of the open chain class invented in Germany by Hoechst in 1947. It is one of a handful of useful synthetic analgesics which were used in the United States for various lengths of time in the 20 or so years after the end of the Second World War but which were withdrawn from the market for various or no known reason and which now are mostly in Schedule I of the United States' Controlled Substances Act of 1970, or in Schedule II but not produced or marketed in the US. Others on this list are ketobemidone (Ketogin), dextromoramide, phenazocine, dipipanone, piminodine (Alvodine), propiram (Algeril), anileridine (Leritine) and alphaprodine (Nisentil).
Benzylmorphine (Peronine) is a semi-synthetic opioid narcotic introduced to the international market in 1896 and that of the United States very shortly thereafter. It is much like codeine, containing a benzyl group attached to the morphine molecule just as the methyl group creates codeine and the ethyl group creates ethylmorphine or dionine. It is about 90% as strong as codeine by weight.
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.
Diethylthiambutene is an opioid analgesic drug developed in the 1950s which was mainly used as an anesthetic in veterinary medicine and continues, along with the other two thiambutenes dimethylthiambutene and ethylmethylthiambutene to be used for this purpose, particularly in Japan. It is now under international control under Schedule I of the UN Single Convention On Narcotic Drugs 1961, presumably due to high abuse potential, although little more information is available. It is listed under Schedule I of the US Controlled Substances Act as a Narcotic and has an ACSCN of 9616 with zero annual manufacturing quota as of 2013.
Tilidine, Leart or tilidate is a synthetic opioid painkiller, used mainly in Belgium, Bulgaria, Germany, Luxembourg, South Africa and Switzerland for the treatment of moderate to severe pain, both acute and chronic. Its onset of pain relief after oral administration is about 10–15 minutes and peak relief from pain occurs about 25–50 minutes after oral administration.
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.
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.
Proheptazine is an opioid analgesic related to pethidine. It was invented in the 1960s.
Benzethidine is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine.
Etoxeridine is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine).
Morpheridine (Morpholinoethylnorpethidine) is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine). It is a strong analgesic with around 4 times the potency of pethidine, and unlike pethidine, does not cause convulsions, although it produces the standard opioid side effects such as sedation and respiratory depression.
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.
Noracymethadol (INN) is a synthetic opioid analgesic related to methadone that was never marketed. In a clinical trial of postpartum patients it was reported to produce analgesia comparable to that of morphine but with less nausea, dizziness, and drowsiness. Other side effects included salivation, ataxia, and respiratory depression that was reversible by naloxone. Similarly to many of its analogues, noracymethadol is a Schedule I controlled substance in the United States with an ACSCN of 9633 and 2013 annual manufacturing quota of 12 grammes. and is also controlled internationally under the United Nations Single Convention on Narcotic Drugs of 1961. The salts known are the gluconate and hydrochloride (0.903).
