Editing Morphine (section)

===Uses and derivatives===
Most of the licit morphine produced is used to make [[codeine]] by methylation.<ref>{{cite web|title=UNODC - Bulletin on Narcotics - 1958 Issue 3 - 005|url=https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1958-01-01_3_page006.html|access-date=11 February 2022|website=United Nations : Office on Drugs and Crime}}</ref> It is also a precursor for a number of drugs including [[heroin]] (3,6-diacetylmorphine), [[hydromorphone]] (dihydromorphinone), and [[oxymorphone]] (14-hydroxydihydromorphinone).<ref>{{Citation |title=Opioids |date=2012 |url=http://www.ncbi.nlm.nih.gov/books/NBK547864/ |work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |access-date=14 November 2023 |place=Bethesda (MD) |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |pmid=31643200}}</ref> Most semi-synthetic opioids, both of the morphine and [[codeine]] subgroups, are created by modifying one or more of the following:{{citation needed|date=February 2020}}<!-- IF ONE SOURCE COVERS ALL POINTS, PLACE ONE SOURCE. IF IT DOES NOT, PLACE RTH REQUIRED SOURCES FOR EACH BULLET POINT. -->
* Halogenating or making other modifications at positions 1 or 2 on the morphine carbon skeleton.
* The methyl group that makes morphine into codeine can be removed or added back, or replaced with another functional group like ethyl and others to make codeine analogues of morphine-derived drugs and vice versa. Codeine analogues of morphine-based drugs often serve as prodrugs of the stronger drug, as in codeine and morphine, hydrocodone and hydromorphone, oxycodone and oxymorphone, nicocodeine and nicomorphine, dihydrocodeine and dihydromorphine, etc.
* Saturating, opening, or other changes to the bond between positions 7 and 8, as well as adding, removing, or modifying functional groups to these positions; saturating, reducing, eliminating, or otherwise modifying the 7–8 bond and attaching a functional group at 14 yields [[hydromorphinol]]; the oxidation of the hydroxyl group to a carbonyl and changing the 7–8 bond to single from double changes codeine into oxycodone.
* Attachment, removal, or modification of functional groups to positions 3 or 6 (dihydrocodeine and related, hydrocodone, nicomorphine); in the case of moving the methyl functional group from position 3 to 6, codeine becomes [[heterocodeine]], which is 72 times stronger, and therefore six times stronger than morphine
* Attachment of functional groups or other modification at position 14 (oxymorphone, oxycodone, naloxone)
* Modifications at positions 2, 4, 5, or 17, usually along with other changes to the molecule elsewhere on the morphine skeleton. Often this is done with drugs produced by catalytic reduction, hydrogenation, oxidation, or the like, producing strong derivatives of morphine and codeine.

Many morphine derivatives can also be manufactured using [[thebaine]] or codeine as a starting material.{{citation needed|date=February 2020}} Replacement of the ''N''-methyl group of morphine with an ''N''-phenylethyl group results in a product that is 18 times more powerful than morphine in its opiate agonist potency.{{citation needed|date=February 2020}} Combining this modification with the replacement of the 6-[[hydroxyl]] with a 6-[[methylene group]] produces a compound some 1,443 times more potent than morphine, stronger than the [[Bentley compounds]] such as [[etorphine]] (M99, the Immobilon tranquilliser dart) by some measures.{{citation needed|date=February 2020}} Closely related to morphine are the opioids morphine-''N''-oxide (genomorphine), which is a pharmaceutical that is no longer in common use;{{citation needed|date=February 2020}} and pseudomorphine, an alkaloid that exists in opium, form as degradation products of morphine.{{citation needed|date=February 2020}}

<!-- The structure-activity relationship of morphine has been extensively studied. THIS SENTENCE IS MEANINGLESS WITHOUT STATEMENT OF WHAT ACTIVITY OR ACTIVITIES ARE UNDER CONSIDERATION. -->As a result of the extensive study and use of this molecule, more than 250 morphine derivatives (also counting codeine and related drugs) have been developed since the last quarter of the 19th century.{{citation needed|date=February 2020}} These drugs range from 25% the analgesic strength of codeine (or slightly more than 2% of the strength of morphine) to several thousand times the strength of morphine, to powerful opioid antagonists, including [[naloxone]] (Narcan), [[naltrexone]] (Trexan), [[diprenorphine]] (M5050, the reversing agent for the Immobilon dart) and [[nalorphine]] (Nalline).{{citation needed|date=February 2020}} Some opioid agonist-antagonists, partial agonists, and inverse agonists are also derived from morphine.{{citation needed|date=February 2020}} The receptor-activation profile of the semi-synthetic morphine derivatives varies widely and some, like [[apomorphine]] are devoid of narcotic effects.{{citation needed|date=February 2020}}