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. 1999;1(2):E4.
doi: 10.1208/ps010204.

Design and synthesis of the CB1 selective cannabinoid antagonist AM281: a potential human SPECT ligand

R Lan  1 , J Gatley, Q Lu, P Fan, S R Fernando, N D Volkow, R Pertwee, A Makriyannis
Affiliations

Design and synthesis of the CB1 selective cannabinoid antagonist AM281: a potential human SPECT ligand

R Lan et al. AAPS PharmSci. 1999.

Abstract

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 [123I]AM281 were developed, and transaxially reconstructed brain SPECT images obtained after continuous infusion of [123I]AM281 in baboons. Thus [123I]AM281 may be suitable for imaging CB1 receptors in humans.

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References

    1. Martin BR. Cellular effects of cannabinoids. Pharmacol Rev. 1986;38:45–74. - PubMed
    1. Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 1988;34:605–613. - PubMed
    1. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature (London) 1993;365:61–65. doi: 10.1038/365061a0. - DOI - PubMed
    1. Barth F, Casellas P, Congy C, Martinez S, Rinaldi M, Anne-Archard G. Pyrazole derivatives, method of preparing them and pharmaceutical compositions in which they are present. US Patent 5,624,941 Apr. 29, 1997.
    1. Rinaldi-Carmona M, Barth F, Héaulme M, Shire D, Calandra B, Congy C, Martinez S, Maruani J, Néliat G, Caput D, Ferrara P, Soubrié P, Breliere JC, Fur G. SR141716A. A potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett. 1994;350:240–244. doi: 10.1016/0014-5793(94)00773-X. - DOI - PubMed

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