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| Trade names | Permonid |
| Other names | Desomorphine, krokodil, dihydrodesoxymorphine, Permonid |
| Addiction liability | Very High |
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| ECHA InfoCard | 100.006.406 |
| Chemical and physical data | |
| Formula | C17H21NO2 |
| Molar mass | 271.360 g·mol−1 |
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Desomorphine[note 1] (or in some formulations known asKrokodil[1][2]) is a semi-syntheticopioid commercialized byRoche, with powerful, fast-acting effects, such assedation andanalgesia.[3][4][5][6] It was first discovered and patented in Germany by a German team working forKnoll in 1920[7] but was not generally recognized. It was later synthesized in 1932 by American chemist Lyndon Frederick Small. Small also successfully patented it in 1934 in the United States.[8] Desomorphine was used inGermany,Austria, andSwitzerland under the brand name Permonid[9] and was described as having a fast onset and a short duration of action, with relatively littlenausea compared to equivalent doses of morphine. Dose for dose it is roughly ten times more potent than morphine, with 1 mg desomorphine being equivalent 10 mg morphine, via the intravenous (IV) or intramuscular (IM) routes.[10]
Desomorphine is amorphine analogue where the 6-hydroxyl group and the 7,8 double bond have been reduced.[8] The traditional synthesis of desomorphine starts fromα-chlorocodide, which is itself obtained by treatingcodeine withthionyl chloride. Bycatalytic reduction, α-chlorocodide givesdihydrodesoxycodeine, which yields desomorphine ondemethylation.[11][12]
A desomorphine product, usually based oncodeine, has been developed as a recreational drug.[13] The product in question is typically a highly impure variant of desomorphine. The scaly sores and necrosis that develop around the injection site has prompted the namekrokodil (Russian for crocodile).
Desomorphine was previously used in Germany, Austria, and Switzerland for the treatment of severe pain. While medical usage of desomorphine was terminated in 1981, during the final years leading up to that it was being used to treat a single patient inBern, Switzerland with a rare illness.[14]: 408–409 While desomorphine was found to be faster acting and more effective than morphine for the rapid relief of severe pain, its shorter duration of action and the relatively more severe respiratory depression produced at equianalgesic doses, as well as a high incidence of other side effects such ashypotension andurinary retention, were felt to outweigh any potential advantages.[15][16]
Desomorphine abuse inRussia attracted international attention in 2010 due to an increase in clandestine production, presumably due to its relatively simple synthesis fromcodeine availableover the counter. Abuse of homemade desomorphine was first reported in Siberia in 2003 when Russia started a major crackdown on heroin production and trafficking, but has since spread throughout Russia and the neighboring former Soviet republics.[14]
The drug can be made fromcodeine andiodine derived from over-the-counter medications andred phosphorus from match strikers,[17] in a process similar to the manufacturing ofmethamphetamine frompseudoephedrine. Like methamphetamine, desomorphine made this way is often contaminated with various agents. The street name in Russia for homemade desomorphine iskrokodil (Russian:крокодил, crocodile), possibly related to the chemical name of the precursorα-chlorocodide, or the resemblance of the skin damage caused by the drug to a crocodile's leather.[14] Due to difficulties in procuringheroin, combined with easy and cheap access to over-the-counter pharmacy products containing codeine in Russia, use of krokodil increased until 2012.[18] In 2012 the Russian federal government introduced new restrictions for the sale of codeine-containing medications. This policy change diminished but did not extinguish krokodil use in Russia.[19] It has been estimated that around 100,000 people use krokodil in Russia and around 20,000 in Ukraine.[18][needs update] One death inPoland in December 2011 was also believed to have been caused by krokodil use, and its use has been confirmed among Russian expatriate communities in other European countries.[20] In 2013 two cases of Krokodil use were reported in the United States.[21] A single case of desomorphine use was reported in Spain in 2014, with the drug consumed orally rather than by injection.[22] There are reports of krokodil use in the United Kingdom.[23][24]
Animal studies comparing pure desomorphine to morphine showed it to have increasedtoxicity, more potentrelief of pain, higher levels ofsedation, decreasedrespiration, and increaseddigestive activity.[25]
Illicitly produced desomorphine is typically far from pure and often contains large amounts oftoxic substances and contaminants as a result of the drug producers neglecting to remove highly toxic reactants and solvents left over fromsynthesis. This neglect could be due to the producers having a limited understanding of chemistry or as a way to avoid the costs of extracting the toxic material. Injecting any such mixture can cause serious damage to theskin,blood vessels,bone, andmuscles, sometimes requiring limb amputation in long-term users.[10] This highly impure product may have received the name ofkrokodil due to the dire effects of the body which can readily be noticed.
Causes of this damage are associated withiodine,phosphorus and other toxic substances that are present after synthesis. Desomorphine producers would use cheap, readily available but relatively toxic and impure solvents such asbattery acid,gasoline or paint thinner during the reaction scheme, without adequately removing them afterwards before distribution. Strong acids and bases such ashydrochloric acid andsodium hydroxide are also employed without measuring thepH of the final solution, and analysis of leftover solutions of "krokodil" in used syringes showed the pH was typically less than 3 (i.e. as acidic as lemon juice).[citation needed] Failure to remove insoluble fillers and binding aids from the codeine tablets used as starting material, as well as co-administration with pharmaceuticals such astropicamide andtianeptine, are also cited as possible contributors to the high toxicity observed in users.
The frequent occurrence of tissue damage and infection among illicit users are what gained the drug its nickname of theflesh-eating drug, or the zombie drug, as homemade versions made under inadequate conditions contain multiple impurities and toxic substances that lead to severe tissue damage and subsequent infection as a direct consequence of use.Gangrene,phlebitis,thrombosis (blood clots),pneumonia,meningitis,septicaemia (blood infection),osteomyelitis (bone infection), liver and kidney damage, brain damage, andHIV/AIDS are common serious adverse health effects observed among users of krokodil.[18] Sometimes, the user will miss the vein when injecting the desomorphine, creating anabscess and causing death of the flesh surrounding the entry-point.[10]
Abuse potential studies of desomorphine in animals had shown that it exhibited limited addiction liability. In monkeys, desomorphine had 10 times the depressant effect of morphine, developed tolerance less rapidly and less completely, and did not lead to the appearance of abstinence symptoms during withdrawal. Studies in rats receiving a daily injection of desomorphine at a constant dose showed that the animals developed tolerance slowly to the depressant effect of desomorphine.[25]
Desomorphine has a molecular weight of 271.35 g/mol and three salts are known:hydrobromide (as in the original Permonid brand; free-base conversion ratio 0.770),hydrochloride (0.881) and sulfate (0.802).[26] Its freebase form is slightly soluble in water (1.425 g/L at 25 °C), although its salts are very water-soluble; its freebase form is also very soluble in most polar organic solvents (likeacetone,ethanol andethyl acetate).[10] Its melting point is 189 °C.[10] It has apKa of 9.69.[10] Desomorphine comes in four isoforms, A, B, C, and D[27] and the latter two appear to be the more researched and used.
Krokodil is made fromcodeine mixed with other substances. The codeine is retrieved from over-the-counter medicine and is then mixed withethanol,gasoline, red phosphorus, iodine,hydrochloric acid andpaint thinner (a mixture ofaliphatic C7 to C12hydrocarbons, eitheropen-chain oralicyclic).[10][28] Toxicnitrogen oxide fumes emerge from the drug when heated.[29]
Desomorphine was first discovered and patented in Germany by a German team working forKnoll in 1920.[7] Desomorphine was later synthesised in the U.S. in 1932 and patented on 13 November 1934.[14] In Russia, desomorphine was declared an illegal narcotic analgesic in 1998. However, while codeine-containing drugs generally have been prescription products in Europe, in Russia they were sold freely over the counter until June 2012.[30] The number of users in Russia was estimated to have reached around one million at the peak of the drug's popularity.[31]
In the US, desomorphine is a Schedule 1 controlled substance, indicating that the United StatesFDA has determined that there are no legal medicinal uses for desomorphine in the United States. It has maintained this status as a controlled substance since 1936.[25] The drug is a Narcotic in Schedule I of theControlled Substances Act 1970 of the United States as drug number (ACSCN) 9055. It is therefore subject to annual aggregate manufacturing quotas in the United States, and in 2014 the quota for desomorphine was 5 grams.[32] It is produced as a hydrochloride (free base conversion ratio 0.85) and sulphate (0.80).[33]
Media in the U.S. andCanada have brought awareness to desomorphine. There have been incidents reported where desomorphine had supposedly been present within either country,[34] but no incidents have been confirmed by any drug testing or analytical results, and desomorphine use in North America is still considered unconfirmed.[35][36]
Media related toDesomorphine at Wikimedia Commons