(S)-AMPA is the active S-enantiomer of AMPA. (S)-AMPA is a potent and highly selective AMPA-type ionotropic glutamate receptor agonist. (S)-AMPA activates AMPA receptors to mediate fast excitatory synaptic transmission in the central nervous system. (S)-AMPA is useful for studies on synaptic transmission, neuroplasticity, and excitotoxicity[1-4].
In vitro, cortical neuron cells were treated with 300μM (S)-AMPA for 5-24h. (S)-AMPA upregulated the transcription of cyclin-dependent kinase 1, cyclin B1, and cyclin D1 genes, induced cell cycle re-entry[5]. Hippocampal neuron cells were treated with 25-50μM (S)-AMPA for 15-30min. (S)-AMPA increased the binding of ubiquitin ligase E3A to potassium voltage-gated channel subfamily D member 2[6]. Cortical culture cells were treated with 10μM (S)-AMPA for 30s. (S)-AMPA induced a rapid increase in intracellular free calcium concentration, triggered a transient increase in network discharge frequency[7].
In vivo, a single intracerebroventricular injection of 1-10nmol per rat (S)-AMPA was administered to rats. (S)-AMPA rapidly induced clonic convulsions. A high dose (10nmol per rat) also induced status epilepticus behaviors including forelimb clonus, rearing, and salivation[8]. A single intra-amygdalar infusion of 2μL 10μM (S)-AMPA was performed in naive CD1 mice. (S)-AMPA induced despair-like behavior in the tail suspension test and forced swimming test[9]. A single microinjection of 0.01875-0.075μg (S)-AMPA into the lateral habenula was performed in male Parkinson's disease model Sprague-Dawley rats. (S)-AMPA induced anxiolytic-like behavior, elevated extracellular dopamine and serotonin levels in the basolateral amygdala[10].
References:[1] Oliveira A, Hodges H, Rezaie P. Excitotoxic lesioning of the rat basal forebrain with S-AMPA: consequent mineralization and associated glial response. Exp Neurol. 2003 Feb;179(2):127-38.
[2] Savell KE, Gallus NVN, Simon RC, et al. Extra-coding RNAs regulate neuronal DNA methylation dynamics. Nat Commun. 2016 Jul 7;7:12091.
[3] Johansen TN, Greenwood JR, Vogensen SB, et al. Structural basis for 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid(AMPA)receptor activation. Pure Appl Chem. 2004;76(5):921-30.
[4] Voss OP. AMPA receptor potentiators: Mechanisms of Neuroplasticity. PhD Thesis, University of Edinburgh. 2007.
[5] Chen MJ, Ng JM, Peng ZF, et al. Gene profiling identifies commonalities in neuronal pathways in excitotoxicity: evidence favouring cell cycle re-activation in concert with oxidative stress. Neurochem Int. 2013 Apr;62(5):719-30.
[6] Hu JH, Malloy C, Liu Y, et al. Activity-dependent degradation of Kv4.2 contributes to synaptic plasticity and behavior in Angelman syndrome model mice. Cell Rep. 2025 May 27;44(115583):1-18.
[7] Klima S, Brill M, Spreng AS, et al. A human stem cell-derived test system for agents modifying neuronal N-methyl-D-aspartate-type glutamate receptor Ca2+-signalling. Arch Toxicol. 2021;95(5):1703-22.
[8] Chiamulera C, Costa S, Valerio E, et al. Domoic acid toxicity in rats and mice after intracerebroventricular administration: comparison with excitatory amino acid agonists. Pharmacol Toxicol. 1992;70(2):115-20.
[9] Shimizu K, Kurosawa N, Seki K, et al. The role of the AMPA receptor and 5-HT3 receptor on aggressive behavior and depressive-like symptoms in chronic social isolation-reared mice. Physiol Behav. 2016;153:70-83.
[10] Zhang J, Wang X, Bernardi RE, et al. Activation of AMPA receptors in the lateral habenula produces anxiolytic effects in a rat model of Parkinson's disease. Front Pharmacol. 2022 Jan 25;13:821975.