Dihydromorphine (Paramorfan, Paramorphan) is a semi-synthetic

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

structurally related to and derived from

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

. The 7,8-double bond in morphine is reduced to a single bond to get dihydromorphine.Rama Rao Nadendla. Principles Of Organic Medicinal Chemistry pp. 215 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 Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) (as in co-dydramol) or aspirin. It was developed in Germany in 1908 a ...

.DrugBank: Dihydromorphine (DB01565)
/ref>Dihydromorphine - PubChem
/ref> 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.

Uses

Medical

Dihydromorphine is used for the management of moderate to severe pain such as that occurring in cancer; however, it is less effective in treating neuropathic pain and is generally considered inappropriate and ineffective for psychological pain.

Research

Dihydromorphine, often labelled with the isotope

tritium Tritium ( or , ) or hydrogen-3 (symbol T or H) is a rare and radioactive isotope of hydrogen with half-life about 12 years. The nucleus of tritium (t, sometimes called a ''triton'') contains one proton and two neutrons, whereas the nucleus of ...

in the form of Hdihydromorphine, is used in scientific research to study binding of the

opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin ...

s in the

nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...

Strength

Dihydromorphine is slightly stronger than morphine as an analgesic with a similar side effect profile. The relative potency of dihydromorphine is about 1.2 times that of morphine. In comparison, the relative potency of

is around 1.2 to 1.75 times that of codeine.

Pharmacology

Dihydromorphine acts as an agonist at the μ-opioid (mu) with a ki value of 2.5nM compared to 4.9nM of

Morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

, δ-opioid (delta) with a ki value of 137nM compared to 273nM of Morphine and κ-opioid (kappa) with a ki value of 223nM compared to 227nM of Morphine. Dihydromorphine is therefore slightly more Mu selective than Morphine . Agonist of the μ-opioid and δ-opioid receptors is largely responsible for the clinical effects of opioids like dihydromorphine with the μ agonism providing more analgesia than the δ.

Pharmacokinetics

Dihydromorphine's onset of action is more rapid than morphine and it also tends to have a longer duration of action, generally 4–7 hours.

Legality

Under the 1961 international

Single Convention on Narcotic Drugs The Single Convention on Narcotic Drugs, 1961 (Single Convention, 1961 Convention, or C61) is an international treaty that controls activities (cultivation, production, supply, trade, transport) of specific narcotic drugs and lays down a syste ...

treaty dihydromorphine is a Schedule I narcotic subject to control, and other countries' laws may vary.

United States

Under the Controlled Substances Act, dihydromorphine is listed as a Schedule I substance along with heroin. In the United States, its role in the production of dihydrocodeine and other related drugs make it a Schedule I substance with one of the higher annual manufacturing quotas granted by the US

Drug Enforcement Administration The Drug Enforcement Administration (DEA; ) is a United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within the U.S. It is the lead agency for domestic en ...

—3300 kilos in 2013; manufacturers, distributors, and importers with the correct DEA license and state permits related thereto are able to use Schedule I drugs in this fashion when they are transformed into something of a lower schedule. The DEA has assigned dihydromorphine and all of its salts, esters, &c the ACSCN of 9145. As with nicomorphine, MDMA, heroin (DEA 2013 production quota: 25 grammes) and the like, dihydromorphine is also used in research such as that mentioned above in properly licensed facilities; Form 225, the most common and least expensive individual researcher's license, does not include Schedule I so the lab must have a higher-level DEA registration As with other licit opioids used for medical purposes in other countries, including even much weaker opioids like nicocodeine, benzylmorphine, and tilidine, the reason for dihydromorphine being in Schedule I is that it was not in medical use in the US at time the Controlled Substances Act of 1970 was drawn up.

Europe

Dihydromorphine is regulated in the same fashion as morphine in Germany under the BtMG, Austrian SMG, and Swiss BtMG, where it is still used as an analgesic. The drug was invented in Germany in 1900 and marketed shortly thereafter. It is often used in Patient Controlled Analgesia units.

Japan

Dihydromorphine and morphine are also used alongside each other in clinical use in Japan and is regulated as such UNODC Bulletin On Narcotics, 1955

References

External links

Various information about dihydromorphine
at the

DrugBank The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets created and maintained by the University of Alberta and The Metabolomics Innovation Centre located in Alberta, Canada. ...

{{Opioidergics Opioid metabolites 4,5-Epoxymorphinans Euphoriants Phenols Cyclohexanols Mu-opioid receptor agonists Semisynthetic opioids