HU 211 is a novel and non-competitive antagonist of NMDA [1].
N-Methyl-D-aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor and only binds to and regulates the NMDA receptor.
HU 211 is a novel and non-competitive NMDA antagonist. In culture neurones, HU 211 inhibited NMDA-mediated neurotoxicity in a dose dependent way with EC50 value of 3.8 µM. Also, HU 211 inhibited [3H]MK-801 binding to rat forebrain membranes in a competitive way with Ki value of 11.0 µM [1]. In rat alveolar macrophage cell line and murine peritoneal macrophages, HU 211 inhibited nitric oxide and TNFα production induced by lipopolysaccharide (LPS) [4].
In a global ischemia gerbil model, HU-211 (4 mg/kg) significantly induced neuroprotection in the CA1 subfield of the hippocampus [2]. In the rat with closed head injury (CHI), HU-211 (5 mg/kg) significantly improved neurological severity score (NSS) and slightly reduced edema. In the Morris water maze, HU-211 significantly improved the abilities impaired by CHI [3]. In BALB/c mice injected with 10 mg/kg LPS, HU-211 reduced lethality to 9 and 67%. In Sprague-Dawley rats, HU-211 abolished the hypotensive response induced by LPS [4].
References:
[1]. Eshhar N, Striem S, Biegon A. HU-211, a non-psychotropic cannabinoid, rescues cortical neurones from excitatory amino acid toxicity in culture. Neuroreport, 1993, 5(3): 237-240.
[2]. Bar-Joseph A, Berkovitch Y, Adamchik J, et al. Neuroprotective activity of HU-211, a novel NMDA antagonist, in global ischemia in gerbils. Mol Chem Neuropathol, 1994, 23(2-3): 125-135.
[3]. Shohami E, Novikov M, Bass R. Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat. Brain Res, 1995, 674(1): 55-62.
[4]. Gallily R, Yamin A, Waksmann Y, et al. Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid. J Pharmacol Exp Ther, 1997, 283(2): 918-924.