D-AP5 is a selective N-methyl-D-aspartate (NMDA) receptor antagonist with a Kd value of 1.4μM[1]. D-AP5 inhibits the glutamate binding site of the NMDA receptor[2]. It can be used to study the role of NMDA receptors in neuropathology, particularly in neuroprotection[3].
In vitro, D-AP5 (30μM) treatment of cortical astrocytes significantly reduces the increase in intracellular Ca2+ concentration induced by synaptically released glutamate by inhibiting NMDA receptors[4]. D-AP5 (20μM) treatment of mouse hippocampal neurons significantly reduces NMDA-induced calcium influx and inhibits neuronal electrical activity, thereby protecting neurons from excitotoxic damage[5].
In vivo, D-AP5 (0.5µg/µL;1µL/h) administered via intracerebroventricular infusion to Lister hooded rats for 14 days significantly affected spatial learning and memory abilities, primarily by inhibiting NMDA receptor-mediated synaptic plasticity mechanisms and the formation of long-term potentiation (LTP)[6]. D-AP5 (5-10 nmol/µL; 0.5µL/h) administered via intracerebroventricular infusion in rats significantly inhibited LTP formation in the hippocampal CA1 region, resulting in memory impairment[7].
References:
[1] Evans R H, Francis A A, Jones A W, et al. The effects of a series of ω‐phosphonic α‐carboxylic amino acids on electrically evoked and excitant amino acid‐induced responses in isolated spinal cord preparations[J]. British journal of pharmacology, 1982, 75(1): 65-75.
[2] Choi D W, Koh J, Peters S. Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists[J]. Journal of Neuroscience, 1988, 8(1): 185-196.
[3] Hwang J Y, Kim Y H, Ahn Y H, et al. N-Methyl-D-aspartate receptor blockade induces neuronal apoptosis in cortical culture[J]. Experimental neurology, 1999, 159(1): 124-130.
[4] Palygin O, Lalo U, Verkhratsky A, et al. Ionotropic NMDA and P2X1/5 receptors mediate synaptically induced Ca2+ signalling in cortical astrocytes[J]. Cell calcium, 2010, 48(4): 225-231.
[5] Benveniste M, Mienville J M, Sernagor E, et al. Concentration-jump experiments with NMDA antagonists in mouse cultured hippocampal neurons[J]. Journal of Neurophysiology, 1990, 63(6): 1373-1384.
[6] Morris R G M, Steele R J, Bell J E, et al. N‐methyl‐d‐aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d‐AP 5 interacts directly with the neural mechanisms of spatial learning[J]. European Journal of Neuroscience, 2013, 37(5): 700-717.
[7] Davis S, Butcher S P, Morris R G. The NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro[J]. Journal of Neuroscience, 1992, 12(1): 21-34.
D-AP5是一种选择性N-甲基-D-天门冬胺酸（NMDA）受体拮抗剂，Kd 值为1.4μM[1]。D-AP5抑制NMDA受体的谷氨酸结合位点[2]。D-AP5可用于研究NMDA受体在神经病理学中的作用，特别是在神经保护方面[3]。
在体外，D-AP5（30μM）处理皮质星形胶质细胞，通过抑制NMDA受体，显著降低了由突触释放的谷氨酸引起的胞内Ca2+浓度的升高[4]。D-AP5（20μM）处理小鼠海马神经元细胞，显著减少了NMDA诱导的钙流入，并抑制神经元电活动，从而保护神经元免受过度兴奋性损伤[5]。
在体内，D-AP5（0.5µg/µL;1µL/h）通过脑室内输注治疗Lister hooded大鼠，持续14天后显著影响了大鼠的空间学习和记忆能力，主要通过抑制NMDA受体介导的突触可塑性机制来实现，抑制了长时程增强（LTP）的形成[6]。D-AP5（5-10 nmol/µL;0.5µL/h）通过脑室内输注治疗大鼠，显著抑制了海马CA1区的LTP形成，表现出记忆功能损伤[7]。