alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid


Summary: An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.

Top Publications

  1. Aizenman C, Cline H. Enhanced visual activity in vivo forms nascent synapses in the developing retinotectal projection. J Neurophysiol. 2007;97:2949-57 pubmed
    ..This suggests that in vivo visual stimulation increases synapses that have a low Pr and that have properties consistent with immature synapses. ..
  2. Caruso A, Di Giorgi Gerevini V, Castiglione M, Marinelli F, Tomassini V, Pozzilli C, et al. Testosterone amplifies excitotoxic damage of cultured oligodendrocytes. J Neurochem. 2004;88:1179-85 pubmed
    ..We conclude that testosterone amplifies excitotoxic damage of oligodendrocytes acting at an early step of the death cascade triggered by AMPA/kainate receptors. ..
  3. Wosik K, Ruffini F, Almazan G, Olivier A, Nalbantoglu J, Antel J. Resistance of human adult oligodendrocytes to AMPA/kainate receptor-mediated glutamate injury. Brain. 2004;127:2636-48 pubmed
    ..The apparent lack of glutamate receptor expression on human OLs and their resistance to AMPA/kainate toxicity should be considered when postulating mechanisms of tissue injury in multiple sclerosis. ..
  4. Williams S. Encoding and decoding of dendritic excitation during active states in pyramidal neurons. J Neurosci. 2005;25:5894-902 pubmed
    ..During active states, therefore, distal excitatory synaptic inputs decisively control the excitatory synaptic output of layer 5 neocortical pyramidal neurons and so powerfully influence network activity in the neocortex. ..
  5. Smith M, Ellis Davies G, Magee J. Mechanism of the distance-dependent scaling of Schaffer collateral synapses in rat CA1 pyramidal neurons. J Physiol. 2003;548:245-58 pubmed
    ..We conclude, therefore, that the main synaptic mechanism involved in the production of distance-dependent scaling of Schaffer collateral synapses is an elevated postsynaptic AMPA receptor density. ..
  6. Michel S, Itri J, Colwell C. Excitatory mechanisms in the suprachiasmatic nucleus: the role of AMPA/KA glutamate receptors. J Neurophysiol. 2002;88:817-28 pubmed
    ..Overall, our data suggest that glutamatergic synaptic transmission mediated by AMPA/KA GluRs play an important role throughout the SCN synaptic circuitry. ..
  7. Pankratov Y, Krishtal O. Distinct quantal features of AMPA and NMDA synaptic currents in hippocampal neurons: implication of glutamate spillover and receptor saturation. Biophys J. 2003;85:3375-87 pubmed
  8. Kopp M, Meissl H, Dehghani F, Korf H. The pituitary adenylate cyclase-activating polypeptide modulates glutamatergic calcium signalling: investigations on rat suprachiasmatic nucleus neurons. J Neurochem. 2001;79:161-71 pubmed
    ..The observed PACAPergic effects provide a broad range of interactions that allow a fine-tuning of the endogenous clock by the integration of 'light' and 'darkness' information on the level of single SCN neurons. ..
  9. Tzounopoulos T, Kim Y, Oertel D, Trussell L. Cell-specific, spike timing-dependent plasticities in the dorsal cochlear nucleus. Nat Neurosci. 2004;7:719-25 pubmed
    ..Thus, synaptic learning rules vary with the postsynaptic cell, and may require the interaction of different transmitter systems. ..

More Information


  1. Chen H, Kintner D, Jones M, Matsuda T, Baba A, Kiedrowski L, et al. AMPA-mediated excitotoxicity in oligodendrocytes: role for Na(+)-K(+)-Cl(-) co-transport and reversal of Na(+)/Ca(2+) exchanger. J Neurochem. 2007;102:1783-1795 pubmed publisher
    ..The latter triggers NCX(rev) and NCX(rev)-mediated overload and compromises mitochondrial function and cellular viability. ..
  2. Hossain M, Russell J, O BRIEN R, Laterra J. Neuronal pentraxin 1: a novel mediator of hypoxic-ischemic injury in neonatal brain. J Neurosci. 2004;24:4187-96 pubmed
    ..05), implicating a role for NP1 in the excitotoxic cascade. Our results show that NP1 induction mediates hypoxic-ischemic injury probably by interacting with and modulating GluR1 and potentially other excitatory glutamate receptors. ..
  3. Vitten H, Reusch M, Friauf E, Löhrke S. Expression of functional kainate and AMPA receptors in developing lateral superior olive neurons of the rat. J Neurobiol. 2004;59:272-88 pubmed
    ..Electrical stimulation of ipsilateral input fibers in the presence of KAR antagonists (NS-102 and GAMS), modulators (WGA), or GYKI 52466 revealed the presence of synaptic KARs in LSO neurons. ..
  4. Pankratov Y, Lalo U, Verkhratsky A, North R. Quantal release of ATP in mouse cortex. J Gen Physiol. 2007;129:257-65 pubmed
    ..Furthermore, the packets of ATP appear to be released from vesicle in a subset of glutamate-containing terminals. ..
  5. Yamane H, Tsuneyoshi Y, Denbow D, Furuse M. N-Methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors involved in the induction of sedative effects under an acute stress in neonatal chicks. Amino Acids. 2009;37:733-9 pubmed publisher
    ..Thus, it is suggested that the iGluRs, NMDA and AMPA, are important in inducing hypnosis and sedation under acute stress in chicks. ..
  6. Johnson M, McIntyre C. Quantifying the neural elements activated and inhibited by globus pallidus deep brain stimulation. J Neurophysiol. 2008;100:2549-63 pubmed publisher
    ..The models suggest that pallidal DBS may have broader network effects than previously realized and the modes of therapy may depend on the relative proportion of GPi and/or GPe efferents that are directly affected by the stimulation. ..
  7. Yoshiyama M, de Groat W. Supraspinal and spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartate glutamatergic control of the micturition reflex in the urethane-anesthetized rat. Neuroscience. 2005;132:1017-26 pubmed
  8. Jensen A, Christesen T, Bølcho U, Greenwood J, Postorino G, Vogensen S, et al. Functional characterization of Tet-AMPA [tetrazolyl-2-amino-3-(3-hydroxy-5-methyl- 4-isoxazolyl)propionic acid] analogues at ionotropic glutamate receptors GluR1-GluR4. The molecular basis for the functional selectivity profile of 2-Bn-Tet-AMPA. J Med Chem. 2007;50:4177-85 pubmed
  9. Reeves R, Thiruchelvam M, Cory Slechta D. Development of behavioral sensitization to the cocaine-like fungicide triadimefon is prevented by AMPA, NMDa, DA D1 but not DA D2 receptor antagonists. Toxicol Sci. 2004;79:123-36 pubmed
    ..As such, TDF may be considered an environmental risk factor for behavioral dysfunctions linked to glutamatergic and dopaminergic systems. ..
  10. Segovia G, Mora F. Dopamine and GABA increases produced by activation of glutamate receptors in the nucleus accumbens are decreased during aging. Neurobiol Aging. 2005;26:91-101 pubmed
    ..These findings suggest that aging changes the interaction between the neurotransmitters glutamate and dopamine and glutamate and GABA in the nucleus accumbens of the freely moving rat. ..
  11. Tong G, Takahashi H, Tu S, Shin Y, Talantova M, Zago W, et al. Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neurons. J Neurophysiol. 2008;99:122-32 pubmed
    ..Taken together, these results show that NR3A subunits contribute to NMDAR responses from both synaptic and extrasynaptic receptors, likely composed of NR1, NR2, and NR3 subunits. ..
  12. Nanou E, El Manira A. A postsynaptic negative feedback mediated by coupling between AMPA receptors and Na+-activated K+ channels in spinal cord neurones. Eur J Neurosci. 2007;25:445-50 pubmed
    ..Thus, Na+ influx via AMPA receptor channels activates K(Na) with properties similar to Slack channels. The AMPA-activated K(Na) may act as an inherent negative feedback mechanism to regulate the homeostasis of excitation. ..
  13. Frost E, Zhou Z, Krasnesky K, Armstrong R. Initiation of oligodendrocyte progenitor cell migration by a PDGF-A activated extracellular regulated kinase (ERK) signaling pathway. Neurochem Res. 2009;34:169-81 pubmed publisher
    ..These findings indicate PDGF-A may act to mobilize OP cells that then respond to distinct directional signals to distribute appropriately within the CNS. ..
  14. Stepulak A, Sifringer M, Rzeski W, Brocke K, Gratopp A, Pohl E, et al. AMPA antagonists inhibit the extracellular signal regulated kinase pathway and suppress lung cancer growth. Cancer Biol Ther. 2007;6:1908-15 pubmed
    ..These findings reveal potential mechanism of antiproliferative action of AMPA antagonists and indicate that this class of compounds may be useful in the therapy of human cancers. ..
  15. Beart P, Lim M, Chen B, Diwakarla S, Mercer L, Cheung N, et al. Hierarchical recruitment by AMPA but not staurosporine of pro-apoptotic mitochondrial signaling in cultured cortical neurons: evidence for caspase-dependent/independent cross-talk. J Neurochem. 2007;103:2408-27 pubmed
  16. Bar Yehuda D, Korngreen A. Cellular and network contributions to excitability of layer 5 neocortical pyramidal neurons in the rat. PLoS ONE. 2007;2:e1209 pubmed
    ..Our results strongly advocate the necessity of redesigning experiments routinely carried out in the quiescent acute brain slice preparation. ..
  17. Taschenberger H, Scheuss V, Neher E. Release kinetics, quantal parameters and their modulation during short-term depression at a developing synapse in the rat CNS. J Physiol. 2005;568:513-37 pubmed
    ..Therefore, a multitude of mechanisms seems to converge on the generation of fast, temporally precise and reliable high-frequency transmission at the mature calyx of Held synapse. ..
  18. Cheung E, Melanson Drapeau L, Cregan S, Vanderluit J, Ferguson K, McIntosh W, et al. Apoptosis-inducing factor is a key factor in neuronal cell death propagated by BAX-dependent and BAX-independent mechanisms. J Neurosci. 2005;25:1324-34 pubmed
    ..Our results demonstrate an important role for AIF in both BAX-dependent and BAX-independent mechanisms of neuronal injury. ..
  19. van den Oever M, Goriounova N, Li K, van der Schors R, Binnekade R, Schoffelmeer A, et al. Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking. Nat Neurosci. 2008;11:1053-8 pubmed publisher
    ..As reexposure to conditioned stimuli is a major cause for heroin relapse, inhibition of GluR2 endocytosis may provide a new target for the treatment of heroin addiction. ..
  20. Chergui K, Svenningsson P, Greengard P. Physiological role for casein kinase 1 in glutamatergic synaptic transmission. J Neurosci. 2005;25:6601-9 pubmed
    ..These results provide the first evidence for a role of CK1 in the regulation of synaptic transmission in the brain. ..
  21. Song D, Wang Z, Marmarelis V, Berger T. Parametric and non-parametric modeling of short-term synaptic plasticity. Part II: Experimental study. J Comput Neurosci. 2009;26:21-37 pubmed publisher
    ..This improved parametric model in turn provides the requisite biological interpretability that the non-parametric model lacks. ..
  22. Furman M, Wang X. Similarity effect and optimal control of multiple-choice decision making. Neuron. 2008;60:1153-68 pubmed publisher
    ..A mechanism is proposed for flexible control of speed-accuracy tradeoff, based on a simple top-down signal to the decision circuit that may vary nonmonotonically with the number of choice alternatives. ..
  23. Chi O, Hunter C, Liu X, Weiss H. Effects of exogenous excitatory amino acid neurotransmitters on blood-brain barrier disruption in focal cerebral ischemia. Neurochem Res. 2009;34:1249-54 pubmed publisher
    ..Any insult increasing the release of excitatory neurotransmitters could further aggravate BBB disruption and brain edema during the ischemic period. ..
  24. Martinez Galan J, Perez Martinez F, Juiz J. Differences in glutamate-mediated calcium responses in the ventral cochlear nucleus and inferior colliculus of the developing rat. Hear Res. 2010;267:46-53 pubmed publisher
  25. Antri M, Auclair F, Albrecht J, Djeudjang N, Dubuc R. Serotoninergic modulation of sensory transmission to brainstem reticulospinal cells. Eur J Neurosci. 2008;28:655-67 pubmed publisher
    ..Our results indicate that 5-HT modulates sensory transmission to lamprey brainstem RS cells. ..
  26. Ito K, Hirooka Y, Hori N, Kimura Y, Sagara Y, Shimokawa H, et al. Inhibition of rho-kinase in the nucleus tractus solitarius enhances glutamate sensitivity in rats. Hypertension. 2005;46:360-5 pubmed
    ..Y-27632 perfusion increased the response to NMDA and AMPA. These results suggest that inhibition of Rho-kinase activity in the NTS enhances glutamate sensitivity in WKY and SHR and might improve impaired glutamate sensitivity in SHR. ..
  27. Amargós Bosch M, Adell A, Artigas F. Antipsychotic drugs reverse the AMPA receptor-stimulated release of 5-HT in the medial prefrontal cortex. J Neurochem. 2007;102:550-61 pubmed
    ..These results suggest that, besides their action in limbic striatum, antipsychotic drugs may attenuate glutamatergic transmission in PFC, possibly by interacting with 5-HT(2A) and/or alpha(1)-adrenoceptors. ..
  28. Shimomura A, Ohkuma M, Iizuka Kogo A, Kohu K, Nomura R, Miyachi E, et al. Requirement of the tumour suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons. Eur J Neurosci. 2007;26:903-12 pubmed
    ..These results are suggestive of APC involvement in the development of glutamatergic synapses. ..
  29. Veruki M, Oltedal L, Hartveit E. Electrical synapses between AII amacrine cells: dynamic range and functional consequences of variation in junctional conductance. J Neurophysiol. 2008;100:3305-22 pubmed publisher
  30. Lopez Huerta V, Tecuapetla F, Guzman J, Bargas J, Galarraga E. Presynaptic modulation by somatostatin in the neostriatum. Neurochem Res. 2008;33:1452-8 pubmed publisher
    ..In contrast, SST does not regulate inhibition coming from interneurons. Because, SST is released by a class of local interneuron, it is concluded that this neuron helps to regulate the selection of motor acts. ..
  31. Fukushima A, Ogura Y, Furuta M, Kakehashi C, Funabashi T, Akema T. Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats. Brain Res. 2015;1622:36-42 pubmed publisher
    ..These results suggest that hippocampal function is not impaired by a ketogenic diet and we speculate that the fat-dependent energy expenditure does not impair visuospatial ability. ..
  32. Ginsberg S. Glutamatergic neurotransmission expression profiling in the mouse hippocampus after perforant-path transection. Am J Geriatr Psychiatry. 2005;13:1052-61 pubmed
    ..The goal is to determine cellular and molecular mechanisms that regulate regenerative and neurodegenerative responses within the adult mouse dentate gyrus after axotomy of the principal glutamatergic input, the perforant path (PP)...
  33. Kamiyama T, Yoshioka N, Sakurai M. Synapse elimination in the corticospinal projection during the early postnatal period. J Neurophysiol. 2006;95:2304-13 pubmed
  34. Brehm L, Greenwood J, Sløk F, Holm M, Nielsen B, Geneser U, et al. Synthesis, theoretical and structural analyses, and enantiopharmacology of 3-carboxy homologs of AMPA. Chirality. 2004;16:452-66 pubmed
    ..The binding mode of (S)-Ethyl-ACPA at iGluR2 was examined by docking to the (S)-ACPA-iGluR2 complex. ..
  35. Pizzul L, Castillo M, Stenström J. Degradation of glyphosate and other pesticides by ligninolytic enzymes. Biodegradation. 2009;20:751-9 pubmed publisher
    ..Moreover, they suggest that the formation of AMPA, the main metabolite of glyphosate degradation found in soils, can be a result of the activity of lignin-degrading enzymes. ..
  36. Bottjer S. Silent synapses in a thalamo-cortical circuit necessary for song learning in zebra finches. J Neurophysiol. 2005;94:3698-707 pubmed
    ..These findings suggest that a developmental decrease in silent synapses within LMAN may represent a neural correlate of behavioral plasticity during song learning. ..
  37. Bilsland L, Nirmalananthan N, Yip J, Greensmith L, Duchen M. Expression of mutant SOD1 in astrocytes induces functional deficits in motoneuron mitochondria. J Neurochem. 2008;107:1271-83 pubmed publisher
    ..These early deficits in mitochondrial function induced by surrounding astrocytes may increase the vulnerability of motoneurons to other neurotoxic mechanisms involved in ALS pathogenesis. ..
  38. Billard J, Rouaud E. Deficit of NMDA receptor activation in CA1 hippocampal area of aged rats is rescued by D-cycloserine. Eur J Neurosci. 2007;25:2260-8 pubmed
    ..Such physiological evidences suggest that this modulation site of NMDAR represents an important target to alleviate cognitive deficits associated with normal ageing. ..
  39. Platania P, Seminara G, Aronica E, Troost D, Vincenza Catania M, Angela Sortino M. 17beta-estradiol rescues spinal motoneurons from AMPA-induced toxicity: a role for glial cells. Neurobiol Dis. 2005;20:461-70 pubmed
  40. Kim S, Lee K. Extracts of Liriopsis tuber protect AMPA induced brain damage and improve memory with the activation of insulin receptor and ERK I/II. Phytother Res. 2008;22:1450-7 pubmed publisher
    ..These results suggest that Liriopsis tuber extracts may exert neuroprotection and memory enhancing effects via activation of the insulin receptor and ERK I/II as well as inhibiting cholinesterase. ..
  41. Aioun J, Rampin O. Anatomical evidence for glutamatergic transmission in primary sensory neurons and onto postganglionic neurons controlling penile erection in rats: an ultrastructural study with neuronal tracing and immunocytochemistry. Cell Tissue Res. 2006;323:359-75 pubmed
    ..The results reveal the presence of Glu in DPN fibers and terminals and suggest that both the spinal cord and the MPG use glutamatergic transmission to control reflexive erections. ..
  42. Boutin H, Chauveau F, Thominiaux C, Gregoire M, James M, Trébossen R, et al. 11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation. J Nucl Med. 2007;48:573-81 pubmed
    ..Although further studies in humans are required, (11)C-DPA-713 represents a suitable alternative to (11)C-PK11195 for PET of PBR as a tracer of neuroinflammatory processes induced by neuronal stress. ..
  43. Pilarski J, Fregosi R. Prenatal nicotine exposure alters medullary nicotinic and AMPA-mediated control of respiratory frequency in vitro. Respir Physiol Neurobiol. 2009;169:1-10 pubmed publisher
  44. Wright C, McCarthy M. Prostaglandin E2-induced masculinization of brain and behavior requires protein kinase A, AMPA/kainate, and metabotropic glutamate receptor signaling. J Neurosci. 2009;29:13274-82 pubmed publisher
  45. Suter K. Control of firing by small (S)-alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid-like inputs in hypothalamic gonadotropin releasing-hormone (GnRH) neurons. Neuroscience. 2004;128:443-50 pubmed
  46. Du J, Wei Y, Liu L, Wang Y, Khairova R, Blumenthal R, et al. A kinesin signaling complex mediates the ability of GSK-3beta to affect mood-associated behaviors. Proc Natl Acad Sci U S A. 2010;107:11573-8 pubmed publisher
    ..The kinesin cargo system may provide valuable novel targets for the development of new therapeutics for mood disorders. ..
  47. Jordan G, McCulloch J, Shahid M, Hill D, Henry B, Horsburgh K. Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation in the mouse as assessed by 14C-2-deoxyglucose autoradiography. Neuropharmacology. 2005;49:254-64 pubmed
  48. Scappaticci A, Kass Simon G. NMDA and GABA B receptors are involved in controlling nematocyst discharge in hydra. Comp Biochem Physiol A Mol Integr Physiol. 2008;150:415-22 pubmed publisher
  49. Essmann C, Martinez E, Geiger J, Zimmer M, Traut M, Stein V, et al. Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors. Nat Neurosci. 2008;11:1035-43 pubmed publisher
    ..In summary, our findings uncover a model of cooperative AMPA receptor and ephrinB reverse signaling at the synapse. ..
  50. Huang S, Liu Y, Liang P. Role of Ca2+ store in AMPA-triggered Ca2+ dynamics in retinal horizontal cells. Neuroreport. 2004;15:2311-5 pubmed
    ..It also suggests that calcium store is an important part contributing to the transient calcium signal. ..
  51. Maeng S, Zarate C, Du J, Schloesser R, McCammon J, Chen G, et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2008;63:349-52 pubmed
    ..NMDA antagonists might exert rapid antidepressant-like effects by enhancing AMPA relative to NMDA throughput in critical neuronal circuits. ..
  52. Hammond R, Lin L, Sidorov M, Wikenheiser A, Hoffman D. Protein kinase a mediates activity-dependent Kv4.2 channel trafficking. J Neurosci. 2008;28:7513-9 pubmed publisher
    ..2 (S552A) prevented the AMPA-induced internalization of Kv4.2. Together, these data demonstrate that Kv4.2 activity-dependent internalization requires PKA phosphorylation of Kv4.2 at serine 522. ..
  53. Rusakov D, Saitow F, Lehre K, Konishi S. Modulation of presynaptic Ca2+ entry by AMPA receptors at individual GABAergic synapses in the cerebellum. J Neurosci. 2005;25:4930-40 pubmed
    ..The results provide the first quantitative description of presynaptic Ca2+ kinetics and its modulation by AMPA receptor activation (most likely via a glutamate spillover-mediated mechanism) at identified GABAergic synapses. ..