Dihydromorphine
Encyclopedia
Dihydromorphine 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.
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 receptor
s 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 enzyme
s 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.)
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
invented in Germany in 1900. In structure, it is very similar to morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, 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
Demethylation
Demethylation is the chemical process resulting in the removal a of methyl group from a molecule.A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms....
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
Thebaine
Thebaine , its name coming from the Greek Θῆβαι, Thēbai, an ancient city in Upper Egypt, is an opiate alkaloid. A minor constituent of opium, thebaine is chemically similar to both morphine and codeine, but has stimulatory rather than depressant effects, causing convulsions similar to strychnine...
.
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.
Dihydromorphine is slightly stronger than morphine as an analgesic with a similar side effect profile. Like metopon
Metopon
Metopon is an opiate analogue that is a methylated derivative of hydromorphone which was invented in 1948 as an analgesic....
, 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
Nicomorphine
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. Nicomorphine was patented as Vilan by Lannacher Heilmittel Ges. m.b.H...
and hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
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
Dihydrocodeine
Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine,...
as well as in some methods of manufacture of hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
, hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
, 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
Nicomorphine
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. Nicomorphine was patented as Vilan by Lannacher Heilmittel Ges. m.b.H...
(Vilan), benzylmorphine
Benzylmorphine
Benzylmorphine is a semi-synthetic opiate narcotic introduced to the international market in 1896 and that of the United States very shortly thereafter...
(Peronine), dihydroisocodeine, acetylmorphone
Acetylmorphone
Acetylmorphone is an opiate analogue that is an acetylated derivative of hydromorphone which was developed in the early 1900s as a potential cough suppressant and analgesic. It is prepared by the acetylation of hydromorphone using either acetyl chloride or acetic anhydride...
, diacetylmorphine (heroin), nicocodeine
Nicocodeine
Nicocodeine is an opiate derivative, closely related to dihydrocodeine and the codeine analogue of nicomorphine developed as a cough suppressant and analgesic. It is not commonly used in most countries, but has activity similar to other opiates. Nicocodeine and nicomorphine were introduced in the...
, acetyldihydrocodeine
Acetyldihydrocodeine
Acetyldihydrocodeine is an opiate derivative discovered in Germany in 1914 and was used as as a cough suppressant and analgesic. It is not commonly used, but has activity similar to other opiates...
, nicodicodeine
Nicodicodeine
Nicodicodeine is an opiate derivative developed as a cough suppressant and analgesic. Synthesized in 1904, it is not commonly used, but has activity similar to other opiates. Nicodicodeine is metabolised in the liver by demethylation to produce 6-nicotinoyldihydromorphine, and subsequently further...
, and others. For this reason, in the United States, dihydromorphine shares a Schedule I designation with these other opioids, under the Controlled Substances Act
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
of 1970. In most other countries, dihydromorphine is classified at the same level as morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, pethidine
Pethidine
Pethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Indonesia); Petidin Dolargan (in Poland);...
and the like where it is available and used; international law and treaties list it as a narcotic
Narcotic
The term narcotic originally referred medically to any psychoactive compound with any sleep-inducing properties. In the United States of America it has since become associated with opioids, commonly morphine and heroin and their derivatives, such as hydrocodone. The term is, today, imprecisely...
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
Drug Enforcement Administration
The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...
.
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
Dihydrocodeine
Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine,...
is 1.17 times the strength of codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
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
Tritium
Tritium is a radioactive isotope of hydrogen. The nucleus of tritium contains one proton and two neutrons, whereas the nucleus of protium contains one proton and no neutrons...
, was amongst tools utilised in the 20th century research, which eventually led to the theory and discovery of opioid receptor
Opioid receptor
Opioid receptors are a group of 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 receptors...
s in the human nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
. Other opioids like buprenorphine
Buprenorphine
Buprenorphine is a semi-synthetic opioid that is used...
, 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
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
converts a percentage of dihydrocodeine into dihydromorphine. The liver enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s 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
Oxymorphone
Oxymorphone or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time...
, nicocodeine
Nicocodeine
Nicocodeine is an opiate derivative, closely related to dihydrocodeine and the codeine analogue of nicomorphine developed as a cough suppressant and analgesic. It is not commonly used in most countries, but has activity similar to other opiates. Nicocodeine and nicomorphine were introduced in the...
to 6-nicotinoylmorphine, and so on).
Other derivates or analogues
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of dihydromorphine are the dihydrocodeine-related family of moderate painkillers and effective cough suppressants (thebacon, nicocodeine, acetyldihydrocodeine, nicodicodeine, and others.)