U-47700, also known as U4, pink heroin, pinky, and pink, is an

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 developed by a team at

Upjohn The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friabl ...

in the 1970s which has around 7.5 times the potency of

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 ...

in animal models. Sample of U-47700

U-47700 is a structural isomer of the earlier opioid

AH-7921 AH-7921 is an opioid analgesic drug selective for the μ-opioid receptor, having around 90% the potency of morphine when administered orally. It was discovered in the 1970s by a team at Allen and Hanburys located in the United Kingdom. The drug ...

and the result of a great deal of work elucidating the

quantitative structure–activity relationship Quantitative structure–activity relationship models (QSAR models) are regression or classification models used in the chemical and biological sciences and engineering. Like other regression models, QSAR regression models relate a set of "predic ...

of the scaffold. Upjohn looked for the key moieties which gave the greatest activity and posted over a dozen patents on related compounds, each optimizing one moiety until they discovered that U-47700 was the most active. U-47700 became the lead compound of selective kappa-opioid receptor ligands such as

U-50488 U-50488 is a drug which acts as a highly selective κ-opioid agonist, but without any μ-opioid antagonist effects. It has analgesic, diuretic and antitussive effects, and reverses the memory impairment produced by anticholinergic Anticholi ...

, U-51754 (containing a pyrrolidine rather than a

dimethylamine Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to aroun ...

substituent) and

U-69,593 U-69,593 is a drug which acts as a potent and selective κ1-opioid receptor agonist. In animal studies it has been shown to produce antinociception, anti-inflammation, anxiolysis (at low doses), respiratory depression, and diuresis, while ...

, which share very similar structures. Although not used medically, the selective kappa ligands are used in research.

Pharmacology

U-47700 is an agonist of the

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

(K_i 11.1 ± 0.4nM) and possesses significantly lower affinity for the

κ-opioid receptor The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind op ...

(K_i 287 ± 24nM) and

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...

(K_i 1220 ± 82nM). U-47700 is approximately 10-fold more potent than morphine in rats, although the binding of U-47700 is 2-4x weaker than morphine at all three opioid receptors. The metabolism of U-47700 in humans involves mono- and didesmethylation followed by hydroxylation. The desmethyl metabolites of U-47700 have negligable affinity for the opioid receptors and are not thought to contribute to the activity of U-47700.

Side effects

U-47700 has never been studied in humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal. Tachycardia was another side effect encountered with U-47700 use. Tolerance and dependence would be expected to develop.

Deaths

Combined consumption of U-47700 with

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 ...

and flubromazepam caused one fatality in Belgium and Germany, respectively. One death was reported in Ireland, another one in Italy. 17 opioid overdoses and several deaths in the United States had initially been associated with U-47700 in April 2016, as of September 2016 at least 15 fatalities were confirmed. By December 2017, at least 46 fatalities had been associated with the use of U-47700. U-47700 was found in combination with fentanyl during the autopsy of the American artist

Prince A prince is a male ruler (ranked below a king, grand prince, and grand duke) or a male member of a monarch's or former monarch's family. ''Prince'' is also a title of nobility (often highest), often hereditary, in some European states. Th ...

in 2016.

Detection in biological fluids

U-47700 may be measured in serum, plasma, blood or urine to monitor for abuse, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Serum or blood U-47700 concentrations are expected to be in a range of 10–250 μg/L in intoxicated patients and 100–1,500 μg/L in deceased victims of acute overdosage. The detection usually involves analysis by

liquid chromatography-mass spectrometry A liquid is a nearly incompressible fluid that conforms to the shape of its container but retains a (nearly) constant volume independent of pressure. As such, it is one of the four fundamental states of matter (the others being solid, gas, a ...

Society and culture

Common street names for U-47700 include pinky, pink, and U4.

Legal status

Following its sale as a

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. D ...

, U-47700 was made illegal in Sweden on January 26, 2016. U-47700 was emergency scheduled in Ohio on May 3, 2016 by

executive order In the United States, an executive order is a directive by the president of the United States that manages operations of the federal government. The legal or constitutional basis for executive orders has multiple sources. Article Two of t ...

of Governor

John Kasich John Richard Kasich Jr. ( ; born May 13, 1952) is an American politician, author, and television news host who served in the U.S. House of Representatives from 1983 to 2001 and as the 69th governor of Ohio from 2011 to 2019. A Republican, Kasic ...

. U-47700 was emergency scheduled in Florida on September 27, 2016 by an emergency rule of Florida Attorney General Pam Bondi. Responding to a perceived threat to public health and safety, the U.S. Drug Enforcement Administration has placed U-47700 into Schedule I of the Controlled Substances Act, effective November 14, 2016. In April 2018, U-47700 was placed into Schedule I indefinitely. U-47700 was placed into Schedule 1 of South Dakota's Controlled Substance Schedule. It was signed by Governor Daugaard on February 9, 2017.

In popular culture

''U-47700'' is the title of a 2021

Dutch Dutch commonly refers to: * Something of, from, or related to the Netherlands * Dutch people () * Dutch language () Dutch may also refer to: Places * Dutch, West Virginia, a community in the United States * Pennsylvania Dutch Country People E ...

sci-fi Science fiction (sometimes shortened to Sci-Fi or SF) is a genre of speculative fiction which typically deals with imaginative and futuristic concepts such as advanced science and technology, space exploration, time travel, parallel universe ...

short film A short film is any motion picture that is short enough in running time not to be considered a feature film. The Academy of Motion Picture Arts and Sciences defines a short film as "an original motion picture that has a running time of 40 minutes ...

by director

Erasmo de la Parra Erasmo is a given name. Notable people with the name include: *Claudio Erasmo Vargas (born 1974), Mexican race walker *Erasmo Carlos (born 1941), Brazilian singer and songwriter *Erasmo Catarino (born 1977), Mexican singer, winner on the TV show ' ...

. In the film, the characters are addicted to a new drug containing the substance U-47700.

References

{{Opioid receptor modulators Synthetic opioids Benzamides Mu-opioid receptor agonists Dimethylamino compounds Chlorobenzenes Designer drugs