Design and synthesis of the CB1 selective cannabinoid antagonist AM281

R X Lan, Q Lu, P S Fan, J Gatley, N D Volkow, S R Fernando, Roger Guy Pertwee, A Makriyannis

Research output: Contribution to journalArticle


In the search for a radioligand capable of imaging cannabinoid CB1 receptors in the living human brain by SPECT (single photon emission computed tomography), N-(morpholin-4-yl)-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM281) was synthesized. This compound is an analog of the potent, CB1 receptor selective antagonist SR141716A [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide]. AM281 bound to brain and spleen membrane preparations (CB1 and CB2 receptors, respectively) with K-i values of 12 nM and 4200 nM, respectively. AM281 also inhibited the response of guinea-pig small intestine preparation to a cannabinoid receptor agonist. Thus, AM281 behaves as a CB1 receptor selective antagonist. Methods for the rapid, high-yield synthesis and purification of [I-123]AM281 were developed, and transaxially reconstructed brain SPECT images obtained after continuous infusion of [I-123]AM281 in baboons. Thus [I-123]AM281 may be suitable for imaging CB1 receptors in humans.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalAAPS PharmSci
Issue number2
Publication statusPublished - Jun 1999


  • AM281
  • cannabinoid CB1 receptor
  • cannabinoid receptor antagonist
  • CB1 selective ligand
  • SPECT image
  • I-123 LABELED AM251
  • SR 141716A
  • SR141716A
  • AM281
  • cannabinoid receptor antagonist
  • CB1 selective ligand

Cite this

Lan, R. X., Lu, Q., Fan, P. S., Gatley, J., Volkow, N. D., Fernando, S. R., ... Makriyannis, A. (1999). Design and synthesis of the CB1 selective cannabinoid antagonist AM281. AAPS PharmSci, 1(2), 39-45.