Dextromoramide (Palfium, Palphium, Jetrium, Dimorlin) 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 states. In many countries dextromoramide is unused, for example the USA, where it is considered a Schedule I drug, alongside cannabis and LSD, as having no medicinal uses. It is still rarely used in Australia and some European countries, but prescription is avoided due to its abuse potential and so use of Palfium is now mainly limited to terminal care.


Dextromoramide was discovered and patented in 1956 by Dr Paul Janssen at Janssen Pharmaceutica, who also discovered fentanyl, another important synthetic opioid, widely used to treat pain and in combination with other drugs as an anaesthetic. Dextromoramide was much favoured by drug abusers in Australia in the 1970s. It has the proprietary name Palfium, though as of mid 2004 the drug was discontinued in the UK due to limited supplies of precursor chemicals.

Medical use

The main advantage of this drug is that it has a fast onset of action when taken orally, and has a high bioavailability which means that oral dosing produces almost as much effect as injection. It also has a relatively low tendency to cause constipation which is a common problem with opioid analgesics used for cancer pain relief, and tolerance to the analgesic effects develops relatively slowly compared to most other short-acting opioids.

However dextromoramide has several disadvantages, firstly that it has a high potential for development of dependence and addiction, even in patients who are taking it as directed for pain relief and have no previous history of drug abuse, and secondly it has a particularly strong tendency to induce respiratory depression, especially in patients who have low opioid tolerance, and so can be dangerous when used outside of a hospital setting. Another disadvantage is that the bioavailability of oral or sublingual formulations can be variable, and so the medicine may work well for one patient, but poorly for another, or even produce different plasma levels of the drug following the same dose taken on different days. This can be especially dangerous as it may encourage patients to deviate from the prescribed dosage. Suppository dosage formulations may therefore be preferable due to more consistent bioavailability. The typical dose is 5mg four hourly for cancer pain - the drug has a short half life comparable with pethidine. Because of its short duration of action it is unsuitable for maintenance treatment, but can be very useful for acute breakthrough pain. Another advantage is that its high affinity for the opioid receptor allows it to still be effective even when the patient is maintained on relatively high doses of strong analgesics such as methadone. Dextromoramide thus fills the role which is more commonly played by hydromorphone in pain treatment in the USA.

Dextromoramide is sometimes also used as a short-acting analgesic for minor surgical procedures. In this case it is administered sublingually and reaches a therapeutic concentration after around 12 minutes. Another application that has been trialled in Holland is prescription of oral dextromoramide as a way to try to reduce injecting drug use in recidivist opioid addicts who continued to abuse heroin despite being maintained on methadone. This saw modest success in reducing illicit drug use among addicts who wished to regain control over their drug use but were unable to cope being maintained on methadone alone.


Dextromoramide is the right-handed isomer of the moramide molecule. The left-handed molecule is called levomoramide, and a mixture of the two is called racemoramide. Its full chemical name is (+)-1-(3-Methyl-4-morpholino-2,2-diphenylbutyryl)pyrrolidine, and its molecular formula: C25H32N2O2, with an atomic weight of ~392.5.

Dextromoramide was discovered during the course of research into a related family of compounds, the α,α-Diphenyl-γ-Dialkyamino-Butyramides, which show no analgesic activity, but are extremely active physiologically as inhibitors of gastric secretions in man. Other drugs from this series show antispasmodic and antihistamine effects, but most research was put into researching analgesics.

The structure-activity relationships of this family of drugs was investigated extensively, with dextromoramide representing the optimisation of several different structural features;

(i) at the 1-amide group only the pyrrolidine and dimethylamide substituents were active, with pyrrolidine being more potent

(ii) the alkyl chain was more potent when methylated, 3-methylation was more potent than 4-methylation, and in the 3-methyl analogues the dextro isomer was more active

(iii) while morpholine, dimethylamine, pyrrolidine and piperidine were all active at the 4-amine group, morpholine was the most active

(iv) any substitution on the phenyl rings reduces activity.

So dextromoramide, with a pyrrolidine ring on the 1-amide position, a dextro methyl group on the 3-position of the alkyl chain, a morpholine ring around the 4-amine group, and both phenyl rings unsubstituted, was by far the most potent out of all the compounds in this series and was the only one that became widely used in medicine (although the racemic mix racemoramide saw some limited use).


  • Den Otter G, Pain control with dextromoramide (pyrrolamidolum, R 875, palfium), Ned Tijdschr Geneeskd. 1958 Aug 23;102(34):1637-41.
  • Lasagna L, De Kornfeld T, Safar P, A clinical trial of dextromoramide, (R 875, SKF D-5137), J Chronic Dis. 1958 Dec;8(6):689-93.

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