Ethylmorphine

Ethylmorphine

Systematic (IUPAC) name
7,8-didehydro-4,5-α-epoxy- 3-ethoxy-17-methylmorphinan-6-α-ol
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	Schedule II (Single-Entity), Schedule III (In Combination Products)
Identifiers
CAS number	76-58-4 Y
ATC code	R05DA01
PubChem	CID 5359271
DrugBank	DB01466
ChemSpider	4514250 Y
UNII	RWO67D87EU Y
Chemical data
Formula	C19H23NO3
Mol. mass	313.391
SMILES	eMolecules & PubChem
InChI InChI=1S/C19H23NO3/c1-3-22-15-7-4-11-10-13-12-5-6-14(21)18-19(12,8-9-20(13)2)16(11)17(15)23-18/h4-7,12-14,18,21H,3,8-10H2,1-2H3/t12-,13+,14-,18-,19-/m0/s1 Y Key:OGDVEMNWJVYAJL-LEPYJNQMSA-N Y
Y(what is this?)  (verify)

Ethylmorphine (also known as codethyline, dionine, and ethyl morphine) is an opiate narcotic analgesic (pain killer).

Ethylmorphine was invented in Germany at Merck in 1884 and was used as a weaker alternative to heroin for all indications. Chemically, ethylmorphine is a morphine molecule with a -OC₂H₅ group substituted for the aromatic 3-OH group. Therefore the closest chemical relative of ethylmorphine is codeine, also known as methylmorphine. Ethylmorphine also has a hydromorphone analogue (ethyldihydromorphinone or 3-ethoxy-7,8-dihydro-morphin-6-one), and a dihydromorphine analogue known as ethyldihydromorphine, although none of them appears to be commercially distributed at the current time.

As is the case with all narcotic analgesics, ethylmorphine is potentially habit-forming and can generate drug dependence of the codeine type. In most countries and internationally ethylmorphine and codeine are regulated much the same way. Like codeine, dihydrocodeine and similar weak opioid drugs, ethylmorphine is listed under the international Single Convention on Narcotic Drugs in Schedule III, which leads to some ethylmorphine preparations being available over the counter in some countries. In the US, ethylmorphine, like its methyl analog codeine, is controlled under the Controlled Substances Act, Schedule II as a pure compound and Schedule III when combined with non-opioid analgesics such as paracetamol (akin to US Schedule III paracetamol/codeine combinations sold under the brand name Tylenol 3/4). In theory, cough syrup containing ethylmorphine is listed in US Schedule V, meaning that it can be bought without prescription in certain states if the patient presents ID and/or the chemist knows the person and the patient signs a dispensary log that is monitored by the DEA. However, there are currently no ethylmorphine-based pharmaceuticals marketed in the US, making this a moot point; codeine-based products, on the other hand, are still relatively common.

Metabolism

After ingestion, ethylmorphine is converted to morphine in the human liver by the CYP450-isozyme CYP2D6, similarly to codeine. Morphine is a powerful analgesic and the main active compound found in naturally occurring opium. Ethylmorphine's metabolism is hindered by ethanol,^[1] which, being a central nervous system depressant, also boosts the drug's sedative effect—creating a potentially dangerous combination as both drugs cause depression of the respiratory system that can be mutually amplified.

Medical uses

Ethylmorphine is used as an antitussive to treat dry cough. It is also a moderately strong analgesic. It is most widely used in ophthalmology for removing inflammation products from the eyes, inducing miosis and relief of various symptoms. Ethylmorphine was once used, as was heroin, to attempt to cure morphine addiction, including being present in patent medicines sold for this purpose. Ethylmorphine is being investigated as a possible substitution agent for maintenance treatment of opioid dependence as it can quell withdrawal symptoms and also has a ceiling effect, i.e. additional doses beyond a certain level produce no extra euphoria.

Dosage

Ethylmorphine is "less potent than morphine" but "more potent than codeine" by a small percentage. Medical oral dosages vary from 5 to 30, even 50 mg. Like codeine and close chemical relatives, ethylmorphine should not be injected directly into the veins as the sudden histamine release can have dangerous impacts, Naturally, all doses are much lower in parenteral use. Ethylmorphine shares codeine's good oral bioavailability and is the fifth- or sixth-most-commonly used drug of the codeine-based semi-synthetic group of moderate to strong narcotic analgesics. This series includes codeine, dihydrocodeine, ethylmorphine, dihydroethylmorphine, benzylmorphine (Peronine), acetyldihydrocodeine, nicocodeine, nicodicodeine, hydrocodone, thebacon, oxycodone, acetylcodone, methyldihydromorphine and others.

The lethal dose is unknown. One source (in Finnish),^[2] however, suggests it to be as low as 500 mg.

Problems

Tolerance to the drug's effects develops fast. That is why ethylmorphine is normally used only as a temporary medicine to treat e.g. cough. Patients may develop addiction. Side effects, which are rare for medical doses but normal for recreational doses, include the classical opiate side-effects: nausea, vomiting, urinary retention, miosis and constipation. Also, some people are hypersensitive or allergic to ethylmorphine and should never take it. Additionally, the same dose of ethylmorphine can have completely different effects on two different people because of large individual differences in metabolism.

Opioids are known of causing severe physical dependence, in addition to psychological addiction. This type of addiction is hard to treat.

Taking ethylmorphine in combination with alcohol or other drugs that have a suppressive effect on the central nervous system boosts both drugs' effects, creating a dangerous combination. Possible outcome is death through respiratory arrest.

In recreational use the most common problem, however, is liver damage and other effects caused by other compounds besides ethylmorphine. Some analgesics with ethylmorphine also contain indometacin (e.g. Indalgin), which is toxic in high doses.

Antidepressants such as fluoxetine (Prozac) inhibit the enzyme that metabolizes ethylmorphine. Taking ethylmorphine while using such an antidepressant may therefore lead to major changes in ethylmorphine's effects. Conversely, barbiturate compounds such as phenobarbitone induce the same enzyme, which rapidly increases the metabolism of ethylmorpine. Other current medications therefore always have to be taken into account when using this compound.

Brand names

Analgesics

• Indalgin (with indometacin)

Antitussives

• Cocillana
• Cosylan
• Feco Syrup
• Solvipect Comp.

Notes

1. ^ Xu, BQ; Aasmundstad, TA; Lillekjendlie, B; Bjørneboe, A; Christophersen, AS; Mørland, J (1997). "Effects of ethanol on ethylmorphine metabolism in isolated rat hepatocytes: characterization by means of a multicompartmental model". Pharmacology & toxicology 80 (4): 171–81. doi:10.1111/j.1600-0773.1997.tb00392.x. PMID 9140136. 
2. ^ Takaisin. Etyylimorfiini (Finnish). Accessed (via the Internet Archive) on February 27, 2010.

External links

• Journal of Analytical Toxicology article on ethylmorphine metabolism