AM251

AM521是有效的大麻素受体1(CB1)拮抗剂,其IC50值与Ki值分别为8 nM和7.49 nM.

大麻素受体(CB1和CB2)属于G蛋白偶联受体,在各种生理过程中起着重要作用,如认知和免疫功能.

AM251抑制大麻素受体1激动剂与拮抗剂结合到大鼠脑膜[1].在海马中,2 μM AM251减弱内源性大麻素对GABA释放的抑制作用[2].1 μM AM 251抑制内源性大麻素信号对中间神经元放电的抑制[3].AM251抑制电压依赖性钠离子通道,降低神经元兴奋性,并抑制兴奋性与抑制性递质释放[4].

在大鼠的肥胖治疗中,AM251引起持续的食欲减退[5].此外,锻炼能使海马大麻素水平升高,促进记忆巩固,但AM251可以扰乱此过程[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.