UR-144

UR-144

UR-144
Systematic (IUPAC) name
(1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone
Clinical data
Legal status
  • Temporary Class Drug (NZ), Illegal in the UK(2013) Schedule 1 in USA
Identifiers
CAS number  N
ATC code ?
PubChem
ChemSpider  N
ChEMBL  N
Chemical data
Formula C21H29NO 
Mol. mass 311.461 g/mol
 N 

UR-144 (TMCP-018, KM-X1, MN-001, YX-17) is a drug invented by Abbott Laboratories,[1] that acts as a selective full agonist of the peripheral cannabinoid receptor CB2, but with much lower affinity for the psychoactive CB1 receptor.

Contents

  • Pharmacology 1
  • History of use 2
  • Detection 3
  • See also 4
  • References 5
  • Further reading 6

Pharmacology

UR-144 has high affinity for the CB2 receptor with a Ki of 1.8 nM but 83x lower affinity for the CB1 receptor with a Ki of 150 nM.[2] Although a later study found its CB1 affinity to be much higher than previously expected, with a Ki of 28.9nM and an EC50 of 1295nM. Chemically it is closely related to other 2,2,3,3-tetramethylcyclopropyl synthetic cannabinoids like A-796,260 and A-834,735 but with a different substitution on the 1-position of the indole core, in these compounds its 1-pentyl group is replaced with alkylheterocycles like 1-(2-morpholinoethyl) and 1-(tetrahydropyran-4-ylmethyl).

History of use

UR-144 has been detected as an ingredient of synthetic cannabis smoking blends in New Zealand, and subsequently banned from sale as a temporary class drug on 6 April 2012.[3] It has also been encountered in smoking blends and subsequently banned in Russia.[4]

The chemical UR-144 has also been banned in the UK in 2013 along with RCS-4 and AM-2201. This is due to two people in Glasgow being admitted to hospital after taking a legal high with the chemicals in it. Another person was admitted to Brighton hospital after overdosing on the drug.

Detection

A forensic standard of UR-144 is available, and the compound has been posted on the Forendex website of potential drugs of abuse.[5] An ELISA immunoassay technique for detecting UR-144 in urine as part of general drug screens has been developed by Tulip Biolabs, Inc. An Homogeneous Immunoassay that runs on most Clinical Chemistry Analyzers and detects several UR and XLR synthetic cannabinoids has been developed and introduced by Immunalysis Inc. Pomona USA.

See also

References

  1. ^ WO application 2006069196, Pace JM, Tietje K, Dart MJ, Meyer MD, "3-Cycloalkylcarbonyl indoles as cannabinoid receptor ligands", published 2006-06-29, assigned to Abbott Laboratories 
  2. ^ Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD (January 2010). "Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity". J. Med. Chem. 53 (1): 295–315.  
  3. ^ Temporary Class Drug Notices. New Zealand Ministry of Health
  4. ^ Sobolevsky T, Prasolov I, Rodchenkov G (October 2012). "Detection of urinary metabolites of AM-2201 and UR-144, two novel synthetic cannabinoids". Drug Test Anal.  
  5. ^ Southern Association of Forensic Scientists http://forendex.southernforensic.org/detail/index/1218

Further reading

  • Poso A, Huffman JW (January 2008). "Targeting the cannabinoid CB2 receptor: modelling and structural determinants of CB2 selective ligands". Br. J. Pharmacol. 153 (2): 335–46.  
  • Chin CL, Tovcimak AE, Hradil VP, Seifert TR, Hollingsworth PR, Chandran P, Zhu CZ, Gauvin D, Pai M, Wetter J, Hsieh GC, Honore P, Frost JM, Dart MJ, Meyer MD, Yao BB, Cox BF, Fox GB (January 2008). "Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI". Br. J. Pharmacol. 153 (2): 367–79.  
  • Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Miller LN, Li L, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD (March 2008). "Indol-3-yl-tetramethylcyclopropyl ketones: effects of indole ring substitution on CB2 cannabinoid receptor activity". J. Med. Chem. 51 (6): 1904–12.