出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/11 20:20:20」(JST)
| Systematic (IUPAC) name | |
|---|---|
| (3S)-3-methyl-4-morpholin-4-yl-2,2-diphenyl-1-pyrrolidin-1-yl-butan-1-one | |
| Clinical data | |
| Trade names | Palfium |
| AHFS/Drugs.com | International Drug Names |
| Pregnancy cat. | C (AU) |
| Legal status | Controlled (S8) (AU) Schedule I (US) |
| Routes | Oral, Intravenous, Insufflation |
| Pharmacokinetic data | |
| Bioavailability | "High" |
| Half-life | 1.5 - 4.7 hours |
| Identifiers | |
| CAS number | 357-56-2 N |
| ATC code | N02AC01 |
| PubChem | CID 92943 |
| DrugBank | DB01529 |
| ChemSpider | 83901 Y |
| UNII | 9S4S6CIY83 Y |
| KEGG | D07287 Y |
| ChEBI | CHEBI:74274 N |
| ChEMBL | CHEMBL431928 N |
| Chemical data | |
| Formula | C25H32N2O2 |
| Mol. mass | 392.534 |
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| N (what is this?) (verify) | |
Dextromoramide (Palfium, Palphium, Jetrium, Dimorlin)[1] is a powerful opioid analgesic approximately three times more potent than morphine but shorter acting.[2] It is subject to drug prohibition regimes, both internationally through UN treaties, and by the criminal law of individual states. It is still rarely used in Australia and some European countries, but prescription is avoided due to its abuse potential and so use of dextromoramide is now mainly limited to terminal care. It is believed to have the least degree of cross tolerance to morphine of all known opioids, which may be of use in long term opioid therapy.
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 users in Australia in the 1970s and the United Kingdom.[3] It has the main proprietary name of Palfium amongst others, though as of mid-2004 the drug was discontinued in the UK due to limited supplies of precursor chemicals. Although this is true, it is believed there was an approximate one year shortage of Dextromoramide and the real reason that Palfium was not put back into production for the UK market is because of how addictive and potent it is as an oral painkiller. Dependence liability is similar to morphine, but with a less severe withdrawal syndrome. The only European countries that now use the brand palfium are the Netherlands, Ireland and Luxembourg
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.[4]
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).[5]
| リンク元 | 「デキストロモラミド」「デキストロモルアミド」 |