Background:

AM521 is a potent cannabinoid 1 (CB1) receptor antagonist with IC50 of 8 nM and Ki of 7.49 nM.

The cannabinoid receptor (CB1 and CB2) is a member of G-protein coupled receptor which plays a significant role in physiologic processes such as cognitive and immune functions.

AM251 inhibited the coupling of cannabinoid 1 receptor agonists and antagonists onto the rat brain membranes [1]. In hippocampus, 2 μm AM 251 reduced the endocannabinoids inhibitory effects on GABA release [2]. 1 μm AM 251 inhibited endocannabinoid-signaled depression of interneuron firing [3]. AM251 reduced neuronal excitability and inhibited excitatory and inhibitory transmitter release via inhibition of voltage-dependent Na+ channels [4].

AM251 caused sustained anorectic effect in rat for obesity treatment [5]. AM251 may also disrupt the training – induced increase of hippocampus cannabinoids level that promotes memory consolidation [6].

参考文献:
[1] Lan, R, Q.  Liu, P. Fan, S. Lin, S. R. Fernando, D. McCallion, R. Pertwee & A. Makriyannis: Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J. Med. Chem. 1999, 42, 769–776.
[2] Willow, M.  & W. A. Catterall: Inhibition of binding of [3H]batrachotoxin A 20-α-benzoate to sodium channels by the anticonvulsant drugs diphenylhydantoin and carbamazepine. Mol. Pharmacol. 1982, 22, 627–635.
[3] Kreitzer, A.  C., A. G. Carter & W. G. Regehr: Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 2002, 34, 787–796.
[4] Liao C, Zheng J, David LS, Nicholson RA.  Inhibition of voltage-sensitive sodium channels by the cannabinoid 1 receptor antagonist AM 251 in mammalian brain.  Basic Clin Pharmacol Toxicol. 2004 Feb;94(2):73-8.
[5] Chambers AP, Sharkey KA, Koopmans HS.  Cannabinoid (CB)1 receptor antagonist, AM 251, causes a sustained reduction of daily food intake in the rat.  Physiol Behav.  2004 Oct 15;82(5):863-9.
[6] de Oliveira Alvares L, de Oliveira LF, Camboim C, Diehl F, Genro BP, Lanziotti VB, Quillfeldt JA.  Amnestic effect of intrahippocampal AM251, a CB1-selective blocker, in the inhibitory avoidance, but not in the open field habituation task, in rats.  Neurobiol Learn Mem. 2005 Mar;83(2):119-24.