Dihydromorphine

Not to be confused with dehydromorphine.

Dihydromorphine

Systematic (IUPAC) name
3,6-dihydroxy- (5α,6α)- 4,5-epoxy- 17-methylmorphinan
Clinical data
Pregnancy cat.	?
Legal status	Schedule I (US)
Routes	Oral, Intravenous, Intranasally, Sublingually
Identifiers
CAS number	1421-28-9 Y
ATC code	None
PubChem	CID 5359421
IUPHAR ligand	1616
DrugBank	DB01565
ChemSpider	4514282 Y
KEGG	C11782 Y
ChEMBL	CHEMBL1500 Y
Synonyms	Dihydromorphine, Paramorphan
Chemical data
Formula	C17H21NO3
Mol. mass	287.354 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C17H21NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,13,16,19-20H,3,5-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1 Y Key:IJVCSMSMFSCRME-KBQPJGBKSA-N Y
Y(what is this?)  (verify)

Dihydromorphine (Paramorfan, DHM, Paramorphan) is a semi-synthetic opioid invented in Germany in 1900. In structure, it is very similar to morphine, the only difference being the reduction of the double bond between positions 7 and 8 in morphine to a single bond. Dihydromorphine can be made by several processes, including hydrogenating morphine or opium or by demethylating either dihydrocodeine or tetrahydrothebaine. Dihydromorphine is available as tablets for oral use, ampoules of solution for injection by various routes, suppositories, and liquids for oral and sublingual use.

Paramorfan/Paramorphan is a trade name for dihydromorphine, as distinguished from Paramorphine, a genericised trade name and/or former scientific name for thebaine.

Dihydromorphine, along with some other semi-synthetic opiates, is sometimes found in trace amounts in opium produced by the latex method, being formed under poorly-understood conditions. The bodies of mammals including humans can also produce small amounts of the substance from ingested or endogenous morphine.^{[citation needed]}

Dihydromorphine is slightly stronger than morphine as an analgesic with a similar side effect profile. Like metopon, dihydromorphine may be less addictive overall and have better bioavailability after oral administration than morphine. The onset of action is more rapid than morphine and it also tends to have a longer duration of action, generally 4–7 hours. Other drugs with faster onset of action such as nicomorphine and hydromorphone also tend to wear off more quickly, with a mean duration of action around 3 hours in most patients.

At the present time, dihydromorphine is most commonly used in Japan, and various European and Asian countries. A United Nations report in 1993 stated increases in use of dihydromorphine in some Central European countries, and, later, WHO and EU reports show the same, although distinction is not made between use of Paramorfan as an analgesic product or the use of dihydromorphine in the manufacture of other drugs. The latter is also the case in the United States, where it is seen exclusively as an intermediate in the manufacture of dihydrocodeine as well as in some methods of manufacture of hydrocodone, hydromorphone, and related drugs.

It is available as the hydrochloride, hydroiodide, picrate, or monohydrate salt, with the former being the form almost exclusively used in pharmaceuticals but the hydroiodide also used especially in making dihydrocodeine hydroiodide (Paracodin). Individuals and organisations are lobbying for the United States to legalise and approve dihydromorphine for use alongside other analgesics. The Usenet newsgroup alt.politics.usa.legalise-dihydromorphine is one example, albeit atypical in its post volume and pattern.

Dihydromorphine was never introduced in the United States, as is the case of many similar drugs invented in Europe in the intense search for stronger cough suppressants, especially to slow the spread of tuberculosis and other airborne diseases in the two decades prior to the First World War such as thebacon, nicomorphine (Vilan), benzylmorphine (Peronine), dihydroisocodeine, acetylmorphone, diacetylmorphine (heroin), nicocodeine, acetyldihydrocodeine, nicodicodeine, and others. For this reason, in the United States, dihydromorphine shares a Schedule I designation with these other opioids, under the Controlled Substances Act of 1970. In most other countries, dihydromorphine is classified at the same level as morphine, pethidine and the like where it is available and used; international law and treaties list it as a narcotic subject to control, and other countries' laws may vary. Its role in the production of dihydrocodeine makes it the Schedule I substance with one of the higher annual manufacturing quotas granted by the US Drug Enforcement Administration.

One scientific controversy deals with the relative strength of dihydromorphine; according to various official sources, is either 50 per cent or 115-120 per cent of the analgesic strength of morphine. Clinical experience points to the latter. In comparison, dihydrocodeine is 1.17 times the strength of codeine and differs from codeine in not having a ceiling effect on analgesia imposed by metabolism—i.e., above a certain point (400 mg in most people), the codeine is wasted. Dihydromorphine has a longer duration of action (6 hours vs 4 hours for morphine).

Dihydromorphine, often labelled with the isotopes iodine-129 and tritium, was amongst tools utilised in the 20th century research, which eventually led to the theory and discovery of opioid receptors in the human nervous system. Other opioids like buprenorphine, morphine and others are similarly used for research on the actions of drugs of this type in various systems of the body.

The human liver converts a percentage of dihydrocodeine into dihydromorphine. The liver enzymes of the cytochrome P450 II-D-6 series accomplish this feat in a way similar to which the liver activates codeine, by demethylating it to morphine (also, hydrocodone to hydromorphone, oxycodone to oxymorphone, nicocodeine to 6-nicotinoylmorphine, and so on).

Other derivates or analogues of dihydromorphine are the dihydrocodeine-related family of moderate painkillers and effective cough suppressants (thebacon, nicocodeine, acetyldihydrocodeine, nicodicodeine, and others.)