UR-144

Summary

UR-144, also known by its aliases TMCP-018, KM-X1, MN-001, and YX-17, is a pharmaceutical developed by Abbott Laboratories. It operates as a selective full agonist of the peripheral cannabinoid receptor CB2 while displaying a significantly reduced affinity for the psychoactive CB1 receptor.

Identifiers

IUPAC name
CAS Number	1199943-44-6
PubChem CID	44626619
ChemSpider	24634882
UNII	1TYA7HVP1B
ChEMBL	ChEMBL571773
CompTox Dashboard (EPA)	DTXSID60152635
Chemical and physical data
Formula	C21H29NO
Molar mass	311.469 g·mol−1

Pharmacology

UR-144 exhibits a notably high affinity for the CB2 receptor, boasting a Ki of 1.8 nM. However, it demonstrates a substantially lower affinity for the CB1 receptor, with a Ki of 150 nM. Regarding activity, UR-144 possesses an EC50 of 421 nM for human CB1 receptors and 72 nM for human CB2 receptors. Notably, UR-144 induces bradycardia and hypothermia in rats when administered at a dose of 10 mg/kg, indicative of mild cannabinoid-like effects.

Chemically, UR-144 is closely related to other 2,2,3,3-tetramethylcyclopropyl synthetic cannabinoids like A-796,260 and A-834,735. However, it distinguishes itself with a unique substitution on the 1-position of the indole core, replacing the 1-pentyl group with alkyl heterocycles such as 1-(2-morpholino ethyl) and 1-(tetrahydropyran-4-ylmethyl).

Legality

• The UK ACMD recommended the inclusion of UR-144 in generic prohibition legislation in October 2012. This recommendation was accepted by the UK Home Office, leading to the classification of UR-144 as a class B drug under The Misuse of Drugs Act 1971 (Amendment) Order 2013, effective February 26, 2013.
• UR-144 was detected in Korea in 2012. It shares significant similarities with compounds like KM-X1, MN-001, YX-17, and Kr-11.
• In New Zealand, UR-144, found in synthetic cannabis smoking blends, was banned from sale as a temporary class drug on April 6, 2012. It has also been encountered in smoking blends and subsequently banned in Russia.
• As of October 2015, UR-144 is classified as a controlled substance in China.
• The Czech Republic has banned UR-144.

Detection

• A forensic standard of UR-144 is available, and the compound has been included on the Forendex website as a potential drug of abuse.
• An ELISA immunoassay technique for detecting UR-144 in urine as part of general drug screens has been developed by Tulip Biolabs, Inc. Additionally, Immunalysis Inc. has introduced a Homogeneous Immunoassay for detecting various UR and XLR synthetic cannabinoids, compatible with most Clinical Chemistry Analyzers.

FAQ

1. What is UR-144?

• UR-144 is a synthetic cannabinoid that acts on the cannabinoid receptors in the human body, particularly CB1 and CB2 receptors. It was initially developed by Abbott Laboratories.

2. How does UR-144 work?

• UR-144 functions as a selective agonist of the peripheral cannabinoid receptor CB2. It has a significantly lower affinity for the psychoactive CB1 receptor. Its effects are mediated through interactions with these receptors.

3. What are the effects of UR-144?

• UR-144 is designed to mimic the effects of natural cannabinoids. This can lead to altered perception, relaxation, and other cannabinoid-like responses. However, its results can vary among individuals and may have associated health risks.

4. Is UR-144 safe for use?

• The safety of UR-144 is a subject of concern. Synthetic cannabinoids can be unpredictable and carry potential health risks. The use of unregulated designer drugs like UR-144 is discouraged.

5. Is UR-144 legal?

• The legality of UR-144 varies by country and jurisdiction. It is crucial to check local laws and regulations, as it is classified as a controlled substance in some regions.

6. How is UR-144 detected or identified?

• Forensic professionals have developed standards for detecting UR-144. It has also been listed on websites that catalogue potential drugs of abuse. Various techniques, such as immunoassays, are available for identifying UR-144 in urine and other samples.

7. Why is UR-144 banned in some countries?

• UR-144 has been banned in several countries due to concerns about its potential health risks and its association with the abuse of synthetic drugs. Regulations have been put in place to control its distribution and use.

8. Where can I find more information about UR-144?

• To learn more about UR-144, its effects, legal status, and potential health risks, consult reputable sources, including government health agencies, substance abuse resources, and scientific literature. Always rely on accurate and up-to-date information.

References

1. In July 2023, Anvisa introduced “RDC Nº 804,” a resolution listing substances under special control, including narcotics and psychotropic compounds, signifying a significant regulatory update in Brazil.
2. The WO application 2006069196, filed by Pace JM, Tietje K, Dart MJ, Meyer MD, and assigned to Abbott Laboratories, pertains to the development of 3-Cycloalkylcarbonyl indoles as cannabinoid receptor ligands, marking a pivotal step in the invention of UR-144.
3. Research led by Frost JM, Dart MJ, Tietje KR, and others, published in January 2010, examined the effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity, contributing to a deeper understanding of UR-144’s pharmacological properties.
4. Banister SD and collaborators conducted an influential study in August 2015, investigating the impact of bioisosteric fluorine in synthetic cannabinoid designer drugs, including UR-144. This research was published in ACS Chemical Neuroscience, shedding light on the role of fluorine substitutions in these compounds.
5. The UK Advisory Council on the Misuse of Drugs issued a report in October 2012, titled “Further consideration of the synthetic cannabinoids,” providing valuable insights into the classification and regulation of synthetic cannabinoids, including UR-144[5].
6. Almada M, Alves P, Fonseca BM, and others conducted research in February 2020, demonstrating that synthetic cannabinoids like JWH-018, JWH-122, UR-144, and the phytocannabinoid THC activate apoptosis in placental cells, highlighting potential health risks associated with these substances.
7. New Zealand’s Ministry of Health has issued Temporary Class Drug Notices, including UR-144, as part of regulatory efforts to control the distribution and use of these substances.
8. Sobolevsky T, Prasolov I, and Rodchenkov G, in their October 2012 study, focused on the detection of urinary metabolites of AM-2201 and UR-144, providing valuable insights into methods for identifying the presence of UR-144 and related compounds.
9. In September 2015, the China Food and Drug Administration issued a significant notice regarding the management of non-medical narcotics and psychotropic substances, reflecting regulatory developments in China.
10. UR-144 is banned in the Czech Republic, and specific measures have been taken to regulate its use.
11. The Southern Association of Forensic Scientists maintains the Forendex website, a valuable resource for identifying potential drugs of abuse. UR-144 is among the substances listed on this platform.