Dihydromorphine

Last updated
Dihydromorphine
Dihydromorphine 2D structure.svg
Dihydromorphine 3D ball.png
Clinical data
Other namesDihydromorphine, Paramorphan
Dependence
liability
High
Addiction
liability
High
Routes of
administration
Oral, Intravenous, Intranasally, Sublingually
ATC code
  • none
Legal status
Legal status
Identifiers
  • 3,6-dihydroxy-(5α,6α)-4,5-epoxy-17-methylmorphinan
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.007.365 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H21NO3
Molar mass 287.359 g·mol−1
3D model (JSmol)
  • O[C@@H]4[C@@H]5Oc1c2c(ccc1O)C[C@H]3N(CC[C@]25[C@H]3CC4)C
  • 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 Yes check.svgY
  • Key:IJVCSMSMFSCRME-KBQPJGBKSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Dihydromorphine (Paramorfan, Paramorphan) is a semi-synthetic opioid structurally related to and derived from morphine. The 7,8-double bond in morphine is reduced to a single bond to get dihydromorphine. [2] 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. [3] [4] [5] 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. [6]

Contents

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. [3] [7]

Research

Dihydromorphine, often labelled with the isotope tritium in the form of [3H]-dihydromorphine, is used in scientific research to study binding of the opioid receptors in the nervous system. [8] [9]

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 dihydrocodeine is around 1.2 to 1.75 times that of codeine. [2]

Pharmacology

Dihydromorphine acts as an agonist at the μ-opioid with a Ki value of 2.5 nM compared to 4.9 nM of morphine, δ-opioid with a Ki value of 137 nM compared to 273 nM of morphine and κ-opioid with a Ki value of 223 nM compared to 227 nM of morphine. Dihydromorphine is therefore slightly more μ-selective than morphine. [3] [4] Agonism 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. [10] [11]

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.[ citation needed ]

Legality

Under the 1961 international Single Convention on Narcotic Drugs treaty dihydromorphine is a Schedule I narcotic subject to control, and other countries' laws may vary. [12]

United States

Under the Controlled Substances Act, dihydromorphine is listed as a Schedule I substance along with heroin. [13] 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: 3300 kilograms 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. [14] The DEA has assigned dihydromorphine and all of its salts, esters, etc. the ACSCN of 9145. As with nicomorphine, MDMA and heroin, dihydromorphine is also used in research in properly licensed facilities. US DEA Form 225, the most common and least expensive individual researcher's license, does not include Schedule I drugs, and so the lab must have a higher-level DEA registration. [15] 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.[ citation needed ]

Europe

Dihydromorphine is regulated in the same fashion as morphine in Germany under the BtMG, [16] Austrian SMG, [17] and Swiss BtMG, where it is still used as an analgesic. [18] The drug was invented in Germany in 1900 and marketed shortly thereafter. It is often used in Patient Controlled Analgesia units. [19] [20]

Japan

Dihydromorphine and morphine are also used alongside each other in clinical use in Japan and is regulated as such [21]

See also

Related Research Articles

<span class="mw-page-title-main">Hydrocodone</span> Opioid drug used in pain relief

Hydrocodone, also known as dihydrocodeinone, is a semi-synthetic opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid and in combination with homatropine methylbromide to relieve cough. It is also available by itself in a long-acting form sold under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration. Hydrocodone is a controlled drug: in the United States a Schedule II Controlled Substance.

<span class="mw-page-title-main">Morphine</span> Pain medication of the opiate family

Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies. It is mainly used as an analgesic. There are numerous methods used to administer morphine: oral; sublingual; via inhalation; injection into a muscle, injection under the skin, or injection into the spinal cord area; transdermal; or via rectal suppository. It acts directly on the central nervous system (CNS) to induce analgesia and alter perception and emotional response to pain. Physical and psychological dependence and tolerance may develop with repeated administration. It can be taken for both acute pain and chronic pain and is frequently used for pain from myocardial infarction, kidney stones, and during labor. Its maximum effect is reached after about 20 minutes when administered intravenously and 60 minutes when administered by mouth, while the duration of its effect is 3–7 hours. Long-acting formulations of morphine are sold under the brand names MS Contin and Kadian, among others. Generic long-acting formulations are also available.

<span class="mw-page-title-main">Narcotic</span> Chemical substance with psycho-active properties

The term narcotic originally referred medically to any psychoactive compound with numbing or paralyzing properties. In the United States, it has since become associated with opiates and opioids, commonly morphine and heroin, as well as derivatives of many of the compounds found within raw opium latex. The primary three are morphine, codeine, and thebaine.

<span class="mw-page-title-main">Hydromorphone</span> Opioid medication used for pain relief

Hydromorphone, also known as dihydromorphinone, and sold under the brand name Dilaudid among others, is a morphinan opioid used to treat moderate to severe pain. Typically, long-term use is only recommended for pain due to cancer. It may be used by mouth or by injection into a vein, muscle, or under the skin. Effects generally begin within half an hour and last for up to five hours. A 2016 Cochrane review found little difference in benefit between hydromorphone and other opioids for cancer pain.

<span class="mw-page-title-main">Pentazocine</span> Opioid medication

Pentazocine, sold under the brand name Talwin among others, is a painkiller used to treat moderate to severe pain. It is believed to work by activating (agonizing) κ-opioid receptors (KOR) and μ-opioid receptors (MOR). As such it is called an opioid as it delivers its effects on pain by interacting with the opioid receptors. It shares many of the side effects of other opioids like constipation, nausea, itching, drowsiness and respiratory depression, but unlike most other opioids it fairly frequently causes hallucinations, nightmares and delusions. It is also, unlike most other opioids, subject to a ceiling effect, which is when at a certain dose no more pain relief is obtained by increasing the dose any further.

<span class="mw-page-title-main">Opioid</span> Psychoactive chemical

Opioids are a class of drugs that derive from, or mimic, natural substances found in the opium poppy plant. Opioids work in the brain to produce a variety of effects, including pain relief. As a class of substances, they act on opioid receptors to produce morphine-like effects.

<span class="mw-page-title-main">Dihydrocodeine</span> Opioid

Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) or aspirin. It was developed in Germany in 1908 and first marketed in 1911.

<span class="mw-page-title-main">Nalbuphine</span> Opioid analgesic

Nalbuphine, sold under the brand names Nubain among others, is an opioid analgesic which is used in the treatment of pain. It is given by injection into a vein, muscle, or fat.

<span class="mw-page-title-main">Butorphanol</span> Opioid analgesic

Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers. Butorphanol is most closely structurally related to levorphanol. Butorphanol is available as the tartrate salt in injectable, tablet, and intranasal spray formulations. The tablet form is only used in dogs, cats and horses due to low bioavailability in humans.

<span class="mw-page-title-main">Levorphanol</span> Opioid analgesic drug

Levorphanol is an opioid medication used to treat moderate to severe pain. It is the levorotatory enantiomer of the compound racemorphan. Its dextrorotatory counterpart is dextrorphan.

<span class="mw-page-title-main">Piritramide</span> Synthetic opioid

Piritramide(R-3365, trade names Dipidolor, Piridolan, Pirium and others) is a synthetic opioid analgesic that is marketed in certain European countries including: Austria, Belgium, Czech Republic, Slovenia, Germany and the Netherlands. It comes in free form, is about 0.75x times as potent as morphine and is given parenterally for the treatment of severe pain. Nausea, vomiting, respiratory depression and constipation are believed to be less frequent with piritramide than with morphine, and it produces more rapid-onset analgesia when compared to morphine and pethidine. After intravenous administration the onset of analgesia is as little as 1–2 minutes, which may be related to its great lipophilicity. The analgesic and sedative effects of piritramide are believed to be potentiated with phenothiazines and its emetic (nausea/vomiting-inducing) effects are suppressed. The volume of distribution is 0.7-1 L/kg after a single dose, 4.7-6 L/kg after steady-state concentrations are achieved and up to 11.1 L/kg after prolonged dosing.

<span class="mw-page-title-main">Thebacon</span> Opioid medication

Thebacon, or dihydrocodeinone enol acetate, is a semisynthetic opioid that is similar to hydrocodone and is most commonly synthesised from thebaine. Thebacon was invented in Germany in 1924, four years after the first synthesis of hydrocodone. Thebacon is a derivative of acetyldihydrocodeine, where only the 6–7 double bond is saturated. Thebacon is marketed as its hydrochloride salt under the trade name Acedicon, and as its bitartrate under Diacodin and other trade names. The hydrochloride salt has a free base conversion ratio of 0.846. Other salts used in research and other settings include thebacon's phosphate, hydrobromide, citrate, hydroiodide, and sulfate.

<span class="mw-page-title-main">Codeine</span> Opiate and prodrug of morphine used to treat pain

Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, Papaver somniferum. It is typically used to treat mild to moderate degrees of pain. Greater benefit may occur when combined with paracetamol (acetaminophen) or a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. Evidence does not support its use for acute cough suppression in children. In Europe, it is not recommended as a cough medicine in those under 12 years of age. It is generally taken by mouth. It typically starts working after half an hour, with maximum effect at two hours. Its effects last for about four to six hours. Codeine exhibits abuse potential similar to other opioid medications, including a risk of addiction and overdose.

<span class="mw-page-title-main">Benzylmorphine</span> Opioid analgesic and cough suppressant drug

Benzylmorphine (Peronine) is a semi-synthetic opioid narcotic introduced to the international market in 1896 and that of the United States very shortly thereafter. It is much like codeine, containing a benzyl group attached to the morphine molecule just as the methyl group creates codeine and the ethyl group creates ethylmorphine or dionine. It is about 90% as strong as codeine by weight.

<span class="mw-page-title-main">Tapentadol</span> Opioid analgesic of benzenoid class

Tapentadol, sold under the brand name Nucynta among others, is an opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs within 32 minutes of oral administration, and lasts for 4–6 hours.

<span class="mw-page-title-main">Dezocine</span> Opioid analgesic

Dezocine, sold under the brand name Dalgan, is an atypical opioid analgesic which is used in the treatment of pain. It is used by intravenous infusion and intramuscular injection.

<span class="mw-page-title-main">Phenazocine</span> Opioid analgesic

Phenazocine is an opioid analgesic drug, which is related to pentazocine and has a similar profile of effects.

<span class="mw-page-title-main">Propiram</span> Opioid analgesic drug

Propiram is a partial μ-opioid receptor agonist and weak μ antagonist analgesic from the ampromide family of drugs related to other drugs such as phenampromide and diampromide. It was invented in 1963 in the United Kingdom by Bayer but was not widely marketed, although it saw some limited clinical use, especially in dentistry. Propiram reached Phase III clinical trials in the United States and Canada.

<span class="mw-page-title-main">Proglumide</span> Chemical compound

Proglumide, sold under the brand name Milid, is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist, which blocks both the CCKA and CCKB subtypes. It was used mainly in the treatment of stomach ulcers, although it has now been largely replaced by newer drugs for this application.

<span class="mw-page-title-main">Opiate</span> Substance derived from opium

An opiate is an alkaloid substance derived from opium. It differs from the similar term opioid in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain. Opiates are alkaloid compounds naturally found in the opium poppy plant Papaver somniferum. The psychoactive compounds found in the opium plant include morphine, codeine, and thebaine. Opiates have long been used for a variety of medical conditions, with evidence of opiate trade and use for pain relief as early as the eighth century AD. Most opiates are considered drugs with moderate to high abuse potential and are listed on various "Substance-Control Schedules" under the Uniform Controlled Substances Act of the United States of America.

References

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