Desomorphine

desomorphine (also known as dihydrodesoxymorphine) is an opioid substance of the morphinan chemical class that produces analgesic, muscle-relaxing, sedative, and euphoric effects when administered.
it is a structural analog of morphine and the psychoactive component of the mixture known as krokodil (also known as crocodile, krok, or croc).

developed by roche in the 1930s, desomorphine first saw use in switzerland under the trade name permonid.
it was described as having a fast onset, a short duration of action, relatively little nausea, and analgesic potency 8 to 10 times higher than morphine.
concerns about its dependence and abuse potential stemming from these properties led it to fall out of clinical use.

desomorphine first emerged in the russian drug scene around 2003 under the term krokodil. the name is a reference to the scaly, green-black skin discoloration frequently noted in its users. its use and prevalence has been attributed to widespread availability of codeine tablets as inexpensive over-the-counter drugs, along with a simple production process that can be done in a kitchen laboratory using iodine, red phosphorus, paint thinner, and hydrochloric acid.

the application of krokodil regularly induces immediate damage to blood vessels, muscles, and bone and can induce multiple organ failure. these severe complications are, however, caused by the toxic byproducts of the home production process rather than desomorphine itself.

it should be noted that the scientific coverage of krokodil is lacking and most of the knowledge concerning krokodil is based on media coverage. a small number of cases involving krokodil use outside of russia, including germany and the united states, have been reported but have failed to be substantiated. as of 2018, the only confirmed reports of krokodil use are from russia.

history and culture

desomorphine was first synthesized and patented in the united states in 1932.
it was originally synthesized with the intention to create an alternative to morphine in terms of tolerance and addiction properties and improve the side effect profile.
however, desomorphine fell short of these expectations and showed an increased dependence potential compared with morphine.

desomorphine was used in switzerland and introduced to the swiss market in 1940 by the company hoffman-la roche, under the registered trade name of permonid. it was used predominantly for postoperative pain due to its fast onset of action and reduced the tendency to cause respiratory depression and nausea.
toward the end of 1952, permonid was withdrawn from the market. notably, the production of permonid was continued in switzerland until 1981 due to the idiosyncratic analgesic needs of a single patient in bern, switzerland, who suffered from a rare disease.

in russia, krokodil is considered an inexpensive and highly addictive substitute for heroin. its name is derived from crocodile (krokodil in russian) and refers to the scaly, green-black skin discoloration frequently noted in its users. krokodil is produced by synthesizing desomorphine from codeine and combining it with other low-cost, easily obtained additives. these additives can include hydrochloric acid, red phosphorus (from matchbook striking surfaces), iodine, gasoline, and paint thinner and have been proposed to underly krokodil’s severe skin and systemic effects. this production process is similar to that used to make street methamphetamine.

since 2003, the prevalence of krokodil use in russia has been increasing rapidly, presumably as a consequence of its low cost and its high dependence potential.

chemistry

desomorphine, a benzylisoquinoline alkaloid, is an opioid of the morphinan class. dorphine and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called phenanthrene. a fourth nitrogen-containing ring is fused to the phenanthrene at r₉ and r₁₃ with the nitrogen member looking at r₁₇ of the combined structure. this structure is called morphinan.

desomorphine (along with other morphinans) contains an ether bridge between two of its rings, connecting r₄ and r₅ through an oxygen group. it contains one hydroxy group (oh-), bound at r₃, and a methyl group located on the nitrogen atom at r₁₇.
it chemically differs from morphine with regard to the absent secondary hydroxy group at r₆ and the saturated double bond.

pharmacology

like other opiates, desomorphine exerts its effects by binding to and activating the μ-opioid receptor as an agonist. this occurs due to the way in which opioids functionally mimic the body’s natural endorphins. endorphins are responsible for analgesia (pain reduction), sleepiness, and feelings of pleasure and enjoyment. they can be released in response to pain, strenuous exercise, orgasm, or excitement.

this mimicking of natural endorphins results in the drug’s euphoric, analgesic (pain relief), and anxiolytic (anti-anxiety) effects.