Ohmefentanyl (also known as β-hydroxy-3-methylfentanyl, OMF and RTI-4614-4) is an extremely potent

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

analgesic drug which selectively binds to the

µ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalin An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are ...

. There are eight possible

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

s of ohmefentanyl. These stereoisomers are among the most potent μ-opioid receptor agonists known, comparable to super-potent

s such as

carfentanil Carfentanil or carfentanyl, sold under the brand name Wildnil, is a very potent opioid analgesic which is used in veterinary medicine to anesthetize large animals such as elephants and rhinoceroses. It is typically administered in this context ...

and

etorphine Etorphine (M99) is a semi-synthetic opioid possessing an analgesic potency approximately 1,000–3,000 times that of morphine. It was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather the r ...

which are only legally used for tranquilizing large animals such as

elephant Elephants are the largest existing land animals. Three living species are currently recognised: the African bush elephant, the African forest elephant, and the Asian elephant. They are the only surviving members of the family Elephantidae ...

s in

veterinary medicine Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...

. In mouse studies, the most active stereoisomer, 3R,4S,βS-ohmefentanyl, was 28 times more powerful as a painkiller than

fentanyl Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocain ...

, the chemical from which it is derived, and 6300 times more powerful than

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

. Ohmefentanyl has three stereogenic centers and eight

stereoisomers In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms ...

, which are named F9201–F9208. Researchers are studying the different pharmaceutical properties of these isomers. The 4″-fluoro analogue (i.e., substituted on the phenethyl ring) of the 3R,4S,βS isomer of ohmefentanyl is one of the most potent

agonists yet discovered, possessing an analgesic potency approximately 18,000 times that of morphine. Other analogues with potency higher than that of ohmefentanyl itself include the 2′-fluoro derivative (i.e., substituted on the aniline phenyl ring), and derivatives where the N-propionyl group was replaced by N-methoxyacetyl or 2-furamide groups, or a carboethoxy group is added to the 4-position of the piperidine ring. The latter is listed as being up to 30,000 times more potent than morphine. Side effects of

analogues are similar to those of fentanyl itself, which include

itching Itch (also known as pruritus) is a Wikt:sensation, sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of Sensory system, sensory experience. Itch has many similarities to pain, ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

and potentially serious respiratory depression, which can be life-threatening. Illicitly used fentanyl analogues have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in

Estonia Estonia, formally the Republic of Estonia, is a country by the Baltic Sea in Northern Europe. It is bordered to the north by the Gulf of Finland across from Finland, to the west by the sea across from Sweden, to the south by Latvia, a ...

in the early 2000s, and novel derivatives continue to appear. Fentanyl numbering

Synthesis

References

External links

* {{Opioidergics Synthetic opioids Piperidines Phenylethanolamines Propionamides Anilides Mu-opioid receptor agonists

Synthesis

See also

References

External links