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 [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 language | English |
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Pages (from-to) | 39-45 |
Number of pages | 7 |
Journal | AAPS PharmSci |
Volume | 1 |
Issue number | 2 |
DOIs | |
Publication status | Published - Jun 1999 |
Keywords
- AM281
- cannabinoid CB1 receptor
- cannabinoid receptor antagonist
- CB1 selective ligand
- SPECT image
- I-123 LABELED AM251
- RAT-BRAIN
- RECEPTOR ANTAGONIST
- SR 141716A
- IN-VIVO
- LOCALIZATION
- RADIOLIGAND
- SR141716A
- BINDING
- AM281
- cannabinoid receptor antagonist
- CB1 selective ligand