| Name | NMDA receptors (protein family or complex) |
|---|---|
| Synonyms | Glutamate [NMDA] receptor; Glutamate [NMDA] receptors; N methyl D aspartate receptor; N methyl D aspartate receptors; NMDA receptor; NMDA receptors |
| Name | 4-aminopyridine |
|---|---|
| CAS | 4-pyridinamine |
| PubMed | Abstract | RScore(About this table) | |
|---|---|---|---|
| 11692027 | Bains JS, Follwell MJ, Latchford KJ, Anderson JW, Ferguson AV: Slowly inactivating conductance (I (D)): a potential target for stroke therapy. Stroke. 2001 Nov;32(11):2624-34. Manipulations that inhibit this current (4-aminopyridine or angiotensin II) increase neuronal excitability and augment cell death after NMDA receptor activation. |
32(0,1,1,2) | Details |
| 17637606 | Lei G, Xia Y, Johnson KM: The role of Akt-GSK-3beta signaling and synaptic strength in phencyclidine-induced neurodegeneration. Neuropsychopharmacology. 2008 May;33(6):1343-53. Epub 2007 Jul 18. Moreover, increasing synaptic strength by either activation of L-type channels with BAY K8644 or potentiation of synaptic NMDA receptors with either a low concentration of or bicuculline plus 4-aminopyridine completely blocks PCP-induced cell death by increasing Akt phosphorylation. |
32(0,1,1,2) | Details |
| 18036781 | Weiczner R, Krisztin-Peva B, Mihaly A: Blockade of AMPA-receptors attenuates 4-aminopyridine seizures, decreases the activation of inhibitory neurons but is ineffective against seizure-related astrocytic swelling. Epilepsy Res. 2008 Jan;78(1):22-32. Epub 2007 Nov 26. Our previous data proved the efficacy of the NMDA-receptor antagonists on the symptoms, survival and neuronal activation in the 4-aminopyridine- (4-AP) induced seizures. |
31(0,1,1,1) | Details |
| 16806307 | Schoffelmeer AN, Hogenboom F, Wardeh G, De Vries TJ: Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core. Neuropharmacology. 2006 Sep;51(4):773-81. Epub 2006 Jun 30. To that end, receptor-mediated inhibition of depolarization (4-aminopyridine)-induced [3H] release and (NMDA) receptor-stimulated [14C] and [3H] release was studied in superfused NAc core slices. |
31(0,1,1,1) | Details |
| 18845540 | Tauskela JS, Fang H, Hewitt M, Brunette E, Ahuja T, Thivierge JP, Comas T, Mealing GA: Elevated synaptic activity preconditions neurons against an in vitro model of ischemia. J Biol Chem. 2008 Dec 12;283(50):34667-76. Epub 2008 Oct 9. Tolerance to otherwise lethal cerebral ischemia in vivo or to - deprivation (OGD) in vitro can be induced by prior transient exposure to preconditioning in this manner activates extrasynaptic and synaptic NMDA receptors and can require bringing neurons to the "brink of death." We considered if this stressful requirement could be minimized by the stimulation of primarily synaptic NMDA receptors. Specifically, exposing cultures to a K (+)-channel blocker, 4-aminopyridine (20-2500 microm), and a (A) receptor antagonist, bicuculline (50 microm) (4-AP/bic), for 1-2 days resulted in potent tolerance to normally lethal OGD applied up to 3 days later. |
3(0,0,0,3) | Details |
| 16962290 | Bandyopadhyay S, Hablitz JJ: NR2B antagonists restrict spatiotemporal spread of activity in a rat model of cortical dysplasia. Epilepsy Res. 2006 Dec;72(2-3):127-39. Epub 2006 Sep 7. Alterations in expression of N-methyl-D-aspartate receptors (NMDARs) containing NR2B subunits have been suggested to play a role in the hyperexcitability seen in this model. The non-selective NMDAR antagonist d-2-amino-5-phosphonvaleric acid (APV, 20 microM) reduced activity evoked in presence of 50 microM 4-aminopyridine (known to increase excitability by enhancing neurotransmitter release) in neocortical slices from control animals whereas Ro 25-6981 (1 microM) did not. |
1(0,0,0,1) | Details |
| 11389202 | Ishikawa T, Takahashi T: Mechanisms underlying presynaptic facilitatory effect of cyclothiazide at the calyx of Held of juvenile rats. J Physiol. 2001 Jun 1;533(Pt 2):423-31. Bath application of cyclothiazide (CTZ, 100 microM) significantly increased the amplitude of EPSCs mediated by alpha-amino-3--5-methyl-4-isoxazolepropionic acid (AMPA) and (NMDA) receptors. The magnitude of inhibition of presynaptic K (+) currents by CTZ (100 microM) was comparable to that by 5 microM 4-aminopyridine (4-AP). |
1(0,0,0,1) | Details |
| 15745945 | Perea G, Araque A: Properties of synaptically evoked astrocyte signal reveal synaptic information processing by astrocytes. J Neurosci. 2005 Mar 2;25(9):2192-203. In turn, astrocyte Ca2+ signal elicited NMDA receptor-mediated currents in pyramidal neurons. |
1(0,0,0,1) | Details |
| 10651867 | Ptak K, Konrad M, Di Pasquale E, Tell F, Hilaire G, Monteau R: Cellular and synaptic effect of substance P on neonatal phrenic motoneurons. Eur J Neurosci. 2000 Jan;12(1):126-38. Pretreatment with the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) decreased the C4 discharge duration and blocked the effect of SP, thus exhibiting an potentiation by SP. In voltage-clamp mode, SP or the NK1 receptor agonist produced an inward current (ISP) which was not significantly reduced by extracellular application of tetraethylammonium, Co2+, 4-aminopyridine or Cs+. |
1(0,0,0,1) | Details |
| 16478664 | Gigout S, Louvel J, Kawasaki H, D'Antuono M, Armand V, Kurcewicz I, Olivier A, Laschet J, Turak B, Devaux B, Pumain R, Avoli M: Effects of gap junction blockers on human neocortical synchronization. Neurobiol Dis. 2006 Jun;22(3):496-508. Epub 2006 Feb 14. First, we examined the effects of GJ blockers (i.e., carbenoxolone, quinine, and quinidine) on the spontaneous synchronous events (duration = 0.2-1.1 s; intervals of occurrence = 3-27 s) generated by neocortical slices obtained from temporal lobe epileptic patients during application of 4-aminopyridine (4AP, 50 muM) and glutamatergic receptor antagonists. Second, we found that slices from patients with focal cortical dysplasia (FCD) could generate in normal medium spontaneous synchronous discharges (duration = 0.4-8 s; intervals of occurrence = 0.5-90 s) that were (i) abolished by NMDA receptor antagonists and (ii) slowed down by carbenoxolone. |
1(0,0,0,1) | Details |
| 14770276 | Wejksza K, Rzeski W, Parada-Turska J, Zdzisinska B, Rejdak R, Kocki T, Okuno E, Kandefer-Szerszen M, Zrenner E, Turski WA: production in cultured bovine aortic endothelial cells. Naunyn Schmiedebergs Arch Pharmacol. 2004 Mar;369(3):300-4. Epub 2004 Feb 10. (KYNA) is a broad-spectrum antagonist at all subtypes of ionotropic glutamate receptors, but is preferentially active at the strychnine-insensitive allosteric site of the (NMDA) receptor and is also a non-competitive antagonist at the alpha7 nicotinic receptor. KYNA production was inhibited by the aminotransferase inhibitor aminooxyacetic acid but was not affected by a depolarising concentration of K (+) or by 4-aminopyridine. |
1(0,0,0,1) | Details |
| 11247993 | Traub RD, Bibbig R, Piechotta A, Draguhn R, Schmitz D: Synaptic and nonsynaptic contributions to giant ipsps and ectopic spikes induced by 4-aminopyridine in the hippocampus in vitro. J Neurophysiol. 2001 Mar;85(3):1246-56. Sufficient antidromic activity in the model can lead to epileptiform bursts, independent of alpha-amino-3--5-methyl-4-isoxazolepropionic acid (AMPA) and (NMDA) receptors, in some principal cells, preceded by IPSPs and spikelets. |
1(0,0,0,1) | Details |
| 10718516 | Barna B, Szasz A, Vilagi I, Szente M: Anticonvulsive effect of AMPA receptor antagonist GYKI 52466 on 4-aminopyridine-induced cortical ictal activity in rat. Brain Res Bull. 2000 Feb;51(3):241-8. It is also supposed that the cortical inhibition which blocks the propagation of epileptiform process might be activated mainly through non-N-methyl-D-aspartate receptors. |
1(0,0,0,1) | Details |
| 11872250 | Santangeli S, Sills GJ, Stone TW, Brodie MJ: Differential effects of remacemide and desglycinyl-remacemide on epileptiform burst firing in the rat hippocampal slice. Neurosci Lett. 2002 Mar 15;321(1-2):33-6. The effects of remacemide and DGR on zero Mg (2+)/4-aminopyridine-induced epileptiform discharges were investigated in the rat hippocampal slice preparation and compared with carbamazepine (CBZ), a prototypic Na (+) channel blocker, and AR-R15896AR, a putative channel blocker. |
0(0,0,0,0) | Details |
| 18037462 | Cheng YC, Wang JJ, Chang LS: B chain is a functional subunit of beta-bungarotoxin for inducing apoptotic death of human neuroblastoma SK-N-SH cells. Toxicon. 2008 Feb;51(2):304-15. Epub 2007 Oct 13. MK801 (an NMDA receptor antagonist), antibodies against NMDA receptor and 4-aminopyridine (a potassium channel blocker) markedly reduced the cytotoxic effects of beta-Bgt, B chain and catalytically inactivated beta-Bgt. |
33(0,1,1,3) | Details |
| 12576146 | Szakacs R, Weiczner R, Mihaly A, Krisztin-Peva B, Zador Z, Zador E: Non-competitive NMDA receptor antagonists moderate seizure-induced c-fos expression in the rat cerebral cortex. Brain Res Bull. 2003 Feb 15;59(6):485-93. We examined the effects of non-competitive glutamate receptor antagonists on seizures elicited by 4-aminopyridine (4-AP), and in particular, on the expression of the transcription factor c-fos induced by these seizures. |
3(0,0,0,3) | Details |
| 10601428 | Nedergaard S: Regulation of action potential size and excitability in substantia nigra compacta neurons: sensitivity to 4-aminopyridine. J Neurophysiol. 1999 Dec;82(6):2903-13. Such APs were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and could be related to non- (NMDA) receptor-mediated spontaneous excitatory postsynaptic potentials (EPSPs). |
1(0,0,0,1) | Details |
| 20220076 | Carriero G, Uva L, Gnatkovsky V, Avoli M, de Curtis M: Independent epileptiform discharge patterns in the olfactory and limbic areas of the in vitro isolated guinea pig brain during 4-aminopyridine treatment. J Neurophysiol. 2010 Mar 10. |
0(0,0,0,0) | Details |
| 18298662 | Luccini E, Romei C, Raiteri L: Glycinergic nerve endings in hippocampus and spinal cord release by different mechanisms in response to identical depolarizing stimuli. J Neurochem. 2008 Mar 12. In the hippocampus, the Ca (2+)-dependent 4-aminopyridine (1 mmol/L)-evoked overflow was five-fold lower than that in spinal cord. |
0(0,0,0,0) | Details |
| 15197743 | Tebano MT, Pintor A, Frank C, Domenici MR, Martire A, Pepponi R, Potenza RL, Grieco R, Popoli P: Adenosine A2A receptor blockade differentially influences excitotoxic mechanisms at pre- and postsynaptic sites in the rat striatum. J Neurosci Res. 2004 Jul 1;77(1):100-7. In rat corticostriatal slices, ZM 241385 (30-100 nM) significantly reduced 4-aminopyridine (4-AP)-induced paired-pulse inhibition (PPI; an index of neurotransmitter release), whereas it worsened the depression of field potential amplitude elicited by 12.5 and 50 microM). |
0(0,0,0,0) | Details |
| 12460247 | Barbarosie M, Louvel J, D'Antuono M, Kurcewicz I, Avoli M: Masking synchronous -mediated potentials controls limbic seizures. Epilepsia. 2002 Dec;43(12):1469-79. PURPOSE: We determined how CA3-driven interictal discharges block ictal activity generated in the entorhinal cortex during bath application of 4-aminopyridine (4AP, 50 microM). RESULTS: 4AP induced (NMDA) receptor-dependent ictal discharges that originated in the entorhinal cortex, disappeared over time, but were reestablished by cutting the Schaffer collateral (n = 20) or by depressing CA3 network excitability with local application of glutamatergic receptor antagonists (n = 5). |
1(0,0,0,1) | Details |
| 16183639 | Lenz G, Avruch J: Glutamatergic regulation of the p70S6 kinase in primary mouse neurons. . J Biol Chem. 2005 Nov 18;280(46):38121-4. Epub 2005 Sep 22. After 12 days in culture, the response to direct glutamatergic activation is attenuated but can be uncovered by suppression of interneurons with bicuculline in the presence of the weak K (+) channel blocker 4-aminopyridine (4-AP). |
0(0,0,0,0) | Details |
| 19359371 | Chapman RJ, Cilia La Corte PF, Asghar AU, King AE: Network-based activity induced by 4-aminopyridine in rat dorsal horn in vitro is mediated by both chemical and electrical synapses. J Physiol. 2009 Jun 1;587(Pt 11):2499-510. Epub 2009 Apr 9. |
0(0,0,0,0) | Details |
| 18675825 | Witkin JM, Baez M, Yu J, Eiler WJ 2nd: mGlu5 receptor deletion does not confer seizure protection to mice. Life Sci. 2008 Aug 29;83(9-10):377-80. Epub 2008 Jul 15. Chemically induced seizures induced by a variety of mechanisms including pentylenetetrazole, cocaine, kainic acid, 4-aminopyridine, strychnine, and did not differentially increase clonic, clonic/tonic, or lethality in WT vs. mGlu5 receptor KO mice. |
0(0,0,0,0) | Details |
| 14581239 | Pankratov YV, Krishtal OA: Distinct quantal features of AMPA and synaptic currents in hippocampal neurons: implication of spillover and receptor saturation. Biophys J. 2003 Nov;85(5):3375-87. Components mediated by alpha-amino-3--5-methylisoxazole-4-proprionic acid (AMPA) and by (NMDA) receptors were separated pharmacologically. Enhancement of transmitter release with 4-aminopyridine caused a significant increase in quantal size of EPSC. |
3(0,0,0,3) | Details |
| 12617942 | Zheng F, Johnson SW: Metabotropic glutamate and muscarinic cholinergic receptor-mediated preferential inhibition of component of transmissions in rat ventral tegmental area. Neuroscience. 2003;116(4):1013-20. Our laboratory recently reported that presynaptic (B) and A (1) receptors mediate a preferential inhibition on N-methyl-D-aspartate receptor-mediated excitatory postsynaptic currents recorded in rat midbrain neurons. Interestingly, the release stimulator 4-aminopyridine (30 microM) and the uptake inhibitor L-anti-endo-3,4-methanopyrrolidine dicarboxylate (300 microM) preferentially increased the amplitude of excitatory postsynaptic currents.Thus, agonists for metabotropic and muscarinic cholinergic receptors act presynaptically to cause a preferential reduction in the component of excitatory synaptic transmissions. |
3(0,0,0,3) | Details |
| 10780983 | Little HJ, Clark A, Watson WP: Investigations into pharmacological antagonism of general anaesthesia. Br J Pharmacol. 2000 Apr;129(8):1755-63. The general anaesthetic effects of ketamine were unaffected by bicuculline; antagonism was seen with 4-aminopyridine and significant potentiation with 300 mg kg (-1) NMDLA (N-methyl-DL- |
0(0,0,0,0) | Details |
| 19643095 | Smith AJ, Tauskela JS, Stone TW, Smith RA: Preconditioning with 4-aminopyridine protects cerebellar granule neurons against excitotoxicity. Brain Res. 2009 Oct 19;1294:165-75. Epub 2009 Jul 28. |
0(0,0,0,0) | Details |
| 18238817 | Li DP, Yang Q, Pan HM, Pan HL: Pre- and postsynaptic plasticity underlying augmented glutamatergic inputs to hypothalamic presympathetic neurons in spontaneously hypertensive rats. J Physiol. 2008 Mar 15;586(6):1637-47. Epub 2008 Jan 31. But the frequency of neither sEPSCs nor mEPSCs stimulated by 4-aminopyridine or differed significantly between WKY and SHR. |
0(0,0,0,0) | Details |
| 14529953 | Roshan-Milani S, Ferrigan L, Khoshnood MJ, Davies CH, Cobb SR: Regulation of epileptiform activity in hippocampus by nicotinic acetylcholine receptor activation. Epilepsy Res. 2003 Sep;56(1):51-65. Bath application of the potassium channel blocker 4-aminopyridine (4AP; 10-50 microM) resulted in the development of spontaneous epileptiform bursting activity in area CA3 that consisted of short duration (257+/-15 ms) field events occurring regularly at a frequency of 0.4+/-0.02 Hz. (10-30 microM; n=31) also potentiated epileptiform bursting induced by reducing (A) receptor-mediated synaptic transmission using 20 microM bicuculline or enhancing NMDA receptor-mediated excitation by lowering extracellular Mg (2+). |
1(0,0,0,1) | Details |
| 15919710 | Manseau F, Danik M, Williams S: A functional glutamatergic neurone network in the medial septum and diagonal band area. J Physiol. 2005 Aug 1;566(Pt 3):865-84. Epub 2005 May 26. Here we show that local glutamatergic neurones can be activated using 4-aminopyridine (4-AP) and the (A) receptor antagonist bicuculline in regular MS/DB slices, or mini-MS/DB slices. The spontaneous glutamatergic responses were mediated by AMPA receptors and, to a lesser extend, NMDA receptors, and were characterized by large, sometimes repetitive activity that elicited bursts of action potentials postsynaptically. |
1(0,0,0,1) | Details |
| 15979855 | Thuault SJ, Brown JT, Calver AR, Collingridge GL, Randall A, Davies CH: Mechanisms contributing to the exacerbated epileptiform activity in hippocampal slices expressing a C-terminal truncated (B2) receptor subunit. Epilepsy Res. 2005 Jun;65(1-2):41-51. Thus, epileptiform bursts that are sensitive to NMDA receptor antagonists (induced by either the (A) receptor antagonist bicuculline (10muM) or removal of extracellular Mg (2+)) were significantly longer in duration in DeltaGB2-Ct slices relative to WT slices. Furthermore, synchronous (A) receptor-mediated potentials recorded in the presence of the potassium channel blocker 4-aminopyridine (4-AP, 100muM) and the ionotropic glutamate receptor antagonists NBQX (20muM) and D-AP5 (50muM) were significantly prolonged in duration in DeltaGB2-Ct versus WT slices. |
1(0,0,0,1) | Details |
| 11600631 | Gonzalez-Burgos G, Barrionuevo G: Voltage-gated channels shape subthreshold EPSPs in layer 5 pyramidal neurons from rat prefrontal cortex. J Neurophysiol. 2001 Oct;86(4):1671-84. Inhibition of K (+) currents by 4-aminopyridine (4-AP) and TEA increased the TTX-sensitive EPSP amplification. |
0(0,0,0,0) | Details |
| 11826078 | Liang Y, Yuan LL, Johnston D, Gray R: signaling at single mossy fiber presynaptic terminals in the rat hippocampus. J Neurophysiol. 2002 Feb;87(2):1132-7. Experiments with alternative lower affinity indicators for Ca (2+) (fura-2FF and green-2) and the transient K (+) channel blocker, 4-aminopyridine were performed to control for the possible saturation of fura-2. |
0(0,0,0,0) | Details |
| 10822151 | Ramakers GM, Pasinelli P, van Beest M, van der Slot A, Gispen WH, De Graan PN: Activation of pre- and postsynaptic protein kinase C during tetraethylammonium-induced long-term potentiation in the CA1 field of the hippocampus. Neurosci Lett. 2000 May 26;286(1):53-6. Tetraethylammonium (TEA) induces a form of long-term potentiation (LTP) that is independent on (NMDA) receptor activation (LTP (K)). |
2(0,0,0,2) | Details |
| 12492433 | D'Arcangelo G, D'Antuono M, Biagini G, Warren R, Tancredi V, Avoli M: Thalamocortical oscillations in a genetic model of absence seizures. . Eur J Neurosci. 2002 Dec;16(12):2383-93. To increase neuronal excitability, and thus to elicit spontaneous field potential activity in vitro, we applied medium containing: (i) zero [Mg2+]; (ii) high [K+] (8.25 mm); or (iii) low concentrations of the K+ channel blocker 4-aminopyridine (4AP, 0.5-1 micro m). Bath application of the (NMDA) receptor antagonist 3,3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate (CPP) abolished slower FPOs in WAG/Rij cortex and thalamus (n = 6) without infuencing fast FPOs recorded in WAG/Rij (n = 6) or NEC slices (n = 4). |
2(0,0,0,2) | Details |
| 12450487 | Avoli M, D'Antuono M, Louvel J, Kohling R, Biagini G, Pumain R, D'Arcangelo G, Tancredi V: Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro. Prog Neurobiol. 2002 Oct;68(3):167-207. These data indicate that in control animals: (i) prolonged, NMDA receptor-dependent epileptiform discharges, resembling electrographic limbic seizures, originate in the entorhinal cortex from where they propagate to the hippocampus via the perforant path-dentate gyrus route; (ii) the initiation and maintenance of these ictal discharges is paradoxically contributed by (mainly type A) receptor-mediated mechanisms; and (iii) CA3 outputs, which relay a continuous pattern of interictal discharge at approximately 1Hz, control rather than sustain ictal discharge generation in entorhinal cortex. |
1(0,0,0,1) | Details |
| 15013053 | Brown JT, Gill CH, Farmer CE, Lanneau C, Randall AD, Pangalos MN, Collingridge GL, Davies CH: Mechanisms contributing to the exacerbated epileptiform activity in hippocampal slices of GABAB1 receptor subunit knockout mice. Epilepsy Res. 2003 Dec;57(2-3):121-36. Deletion of the GABAB1 receptor subunit had no effect on a range of passive membrane properties of CA3 pyramidale neurones, non-synaptic epileptiform field bursting and spreading depression recorded in 6mM K+/Ca2+-free medium, and inter-ictal synaptically-induced epileptiform activity induced by 100 microM 4-aminopyridine (4-AP). Specifically, enhancement of (NMDA) receptor triggered synaptic processes, arising from the loss of the GABAB receptor-mediated inhibitory postsynaptic potential (IPSP, together with a possible promotion of depolarising IPSPs due to the removal of GABAB autoreceptor function) is likely to underlie these effects. |
1(0,0,0,1) | Details |
| 14654096 | Avoli M, Benini R, de Guzman P, Omar A: GABA (B) receptor activation and limbic network ictogenesis. Neuropharmacology. 2004 Jan;46(1):43-51. Rat brain slices containing interconnected hippocampus and entorhinal cortex (EC) responded to 4-aminopyridine (50 microM) application by generating: (i) CA3-driven interictal discharges that propagated to the EC; and (ii) N-methyl-D-aspartic acid receptor-dependent ictal events originating in EC (cf. Hence, under control conditions, EC ictogenesis depends on NMDA receptor function and is controlled by CA3-driven output activity; in contrast, following GABA (B) receptor activation EC excitability is depressed to a greater extent than CA3, which leads to non- glutamatergic receptor-mediated ictogenesis in CA3. |
1(0,0,0,1) | Details |
| 17910585 | Cepeda C, Andre VM, Wu N, Yamazaki I, Uzgil B, Vinters HV, Levine MS, Mathern GW: Immature neurons and networks may contribute to epileptogenesis in pediatric cortical dysplasia. Epilepsia. 2007;48 Suppl 5:79-85. Cortical dysplasia (CD), a frequent pathological substrate of pediatric epilepsy surgery patients, has a number of similarities with immature cortex, such as reduced Mg2+ sensitivity of (NMDA) receptors and the persistence of subplate-like neurons and undifferentiated cells. Evoked synaptic responses mediated by were also prominent, and bath application of 4-aminopyridine induced rhythmic depolarizations that were blocked by bicuculline. |
1(0,0,0,1) | Details |
| 15716411 | Xu J, Kang N, Jiang L, Nedergaard M, Kang J: Activity-dependent long-term potentiation of intrinsic excitability in hippocampal CA1 pyramidal neurons. J Neurosci. 2005 Feb 16;25(7):1750-60. Induction of LTP-IE was blocked by the NMDA receptor antagonist APV, intracellular BAPTA, the CaM kinase inhibitors KN-62 and autocamtide-2-related inhibitory peptide, and the protein synthesis inhibitors emetine and anisomycin. |
1(0,0,0,1) | Details |
| 16262635 | Ruscheweyh R, Sandkuhler J: Long-range oscillatory Ca2+ waves in rat spinal dorsal horn. Eur J Neurosci. 2005 Oct;22(8):1967-76. However, increasing neuronal excitability by application of 4-aminopyridine after pretreatment of the slice with blockers of (RS)-alpha-amino-3--5-methyl-4-isoxazolepropionic acid (AMPA)/kainate, (GABA)(A) and glycine receptors evoked repetitive Ca2+ waves in dorsal horn. The Ca2+ waves were associated with large depolarizing shifts of the membrane potential of participating neurons and were most likely synaptically mediated because they were abolished by blockade of action potentials or (NMDA) receptors. |
2(0,0,0,2) | Details |
| 11401416 | Koyuncuoglu H, Nurten A, Enginar N, Ozerman B, Kara I: The effects of different 4-aminopyridine and morphine combinations on the intensity of morphine abstinence. Pharmacol Res. 2001 Mar;43(3):245-50. The administration of 4-AP before M appeared to intensify the development of dependence, and was most probably due to the Ca2+-induced inactivation of NMDA receptors as a result of excess release of GLU when the 4-AP took effect. |
2(0,0,0,2) | Details |
| 16109411 | Martin ED, Cena V, Pozo MA: Cholinergic modulation of status epilepticus in the rat barrel field region of primary somatosensory cortex. Exp Neurol. 2005 Nov;196(1):120-5. Epub 2005 Aug 16. Electrocortical and unitary extracellular field recording in the rat S1BF region was used to assess abnormal epileptiform activity induced by intracerebral application of 4-aminopyridine (4-AP). The application of the glutamatergic NMDA receptor antagonist D (-)-2-amino-5-phosphonopentanoic acid (AP5) strongly increased the seizure-onset latency. |
2(0,0,0,2) | Details |
| 12941378 | Ayala GX, Tapia R: Expression of heat shock protein 70 induced by 4-aminopyridine through -mediated excitotoxic stress in rat hippocampus in vivo. Neuropharmacology. 2003 Oct;45(5):649-60. The (NMDA) receptor antagonists MK-801 and (3-phosphonopropyl)-piperazine-2-carboxylic acid prevented the seizures, the neurodegeneration and the expression of HSP70. |
1(0,0,0,1) | Details |
| 18665350 | Ristori C, Cammalleri M, Martini D, Pavan B, Liu Y, Casini G, Dal Monte M, Bagnoli P: Involvement of the cAMP-dependent pathway in the reduction of epileptiform bursting caused by somatostatin in the mouse hippocampus. Naunyn Schmiedebergs Arch Pharmacol. 2008 Dec;378(6):563-77. Epub 2008 Jul 30. Using a well-established model of epileptiform activity induced by Mg (2+)-free medium with 4-aminopyridine [0 Mg (2+)/4-aminopyridine (4-AP)] in mouse hippocampal slices, we demonstrated that protein kinase A (PKA)-related signaling is upregulated by hippocampal bursting and that treatment with SRIF normalizes this upregulation. We also demonstrated that the SRIF-induced inhibition of PKA impairs phosphorylation of the NMDA receptor subunit NR1. |
1(0,0,0,1) | Details |
| 12126879 | Gulyas-Kovacs A, Doczi J, Tarnawa I, Detari L, Banczerowski-Pelyhe I, Vilagi I: Comparison of spontaneous and evoked epileptiform activity in three in vitro epilepsy models. Brain Res. 2002 Aug 2;945(2):174-80. Rat neocortical slices express spontaneous epileptiform activity after incubation with (A) receptor blocker bicuculline (BIC, 20 microM), with potassium channel blocker 4-aminopyridine (4-AP, 50 microM) or in Mg (2+)-free medium (LMG). The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV, 25 microM) abolished the LMG induced spontaneous epileptiform activity and significantly reduced the frequency of the epileptiform discharges in BIC and 4-AP. |
1(0,0,0,1) | Details |
| 18789952 | Ayala GX, Tapia R: HSP70 expression protects against hippocampal neurodegeneration induced by endogenous in vivo. Neuropharmacology. 2008 Dec;55(8):1383-90. Epub 2008 Sep 9. The K+ channel blocker 4-aminopyridine (4-AP) stimulates the release of from nerve endings and induces seizures and neurodegeneration when perfused by microdialysis in rat hippocampus. All these effects of 4-AP are prevented by the NMDA receptor antagonists 3-phosphonopropyl-piperazine-2-carboxilic acid (CPP) and (+) 5-methyl-10,11-dyhydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK-801), indicating that they are due to NMDA receptor overactivation by excessive extracellular synaptic |
1(0,0,0,1) | Details |
| 16364298 | Tovar-y-Romo LB, Tapia R: Cerebral neurons of transgenic ALS mice are vulnerable to release stimulation but not to increased extracellular due to transport blockade. Exp Neurol. 2006 Jun;199(2):281-90. Epub 2005 Dec 20. Using microdialysis in vivo, we tested the effects of the transport inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (PDC) and of 4-aminopyridine (4-AP), which stimulates release from nerve endings, in the hippocampus and motor cortex of wild type (WT) and transgenic SOD1/G93A mice, an established model of FALS. These effects were similar in both WT and G93A mice, and, in both groups, they were prevented by the previous systemic administration of the NMDA receptor antagonist MK-801. |
1(0,0,0,1) | Details |
| 12849742 | Benini R, D'Antuono M, Pralong E, Avoli M: Involvement of amygdala networks in epileptiform synchronization in vitro. Neuroscience. 2003;120(1):75-84. Bath application of the convulsant 4-aminopyridine (50 microM) to slices (n=12) with reciprocally connected areas, induced short-lasting interictal-like epileptiform discharges that (i) occurred at intervals of 1.2-2.8 s, (ii) originated in CA3, and (iii) spread to EC and BLA. NMDA receptor antagonism (n=6) abolished ictal-like discharges and reduced the duration of the slow interictal-like events. |
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| 11311981 | Sequeira SM, Malva JO, Carvalho AP, Carvalho CM: Presynaptic N-methyl-D-aspartate receptor activation inhibits neurotransmitter release through formation in rat hippocampal nerve terminals. Brain Res Mol Brain Res. 2001 Apr 18;89(1-2):111-8. dose-dependently inhibited the release of evoked by 4-aminopyridine (IC (50)=155 microM), and this effect was reversed by the N-methyl-D-aspartate receptor antagonist D-(-)-2-amino-5-phosphopentanoic acid and by the synthase inhibitor, L-nitroarginine, in synaptosomes isolated from whole hippocampus, CA3 and CA1 areas, but not from the dentate gyrus. |
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| 20164347 | Leveille F, Papadia S, Fricker M, Bell KF, Soriano FX, Martel MA, Puddifoot C, Habel M, Wyllie DJ, Ikonomidou C, Tolkovsky AM, Hardingham GE: Suppression of the intrinsic apoptosis pathway by synaptic activity. J Neurosci. 2010 Feb 17;30(7):2623-35. We find that enhanced firing activity suppresses expression of the proapoptotic BH3-only member gene Puma in a NMDA receptor-dependent, p53-independent manner. |
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| 10779701 | Kovacs I, Szarics E, Skuban N, Kardos J: Deramciclane inhibits N-methyl-D-aspartate receptor function. . Brain Res Bull. 2000 May 1;52(1):39-44. |
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| 19445932 | Vilagi I, Dobo E, Borbely S, Czege D, Molnar E, Mihaly A: Repeated 4-aminopyridine induced seizures diminish the efficacy of glutamatergic transmission in the neocortex. Exp Neurol. 2009 Sep;219(1):136-45. Epub 2009 May 13. The NMDA receptor antagonist exerted somewhat stronger effect in the slices from convulsing animals. 4-AP pretreatment resulted in the attenuation of kainate induced Co2+ uptake, which suggests either reduction in non-NMDA receptors numbers or reduction in their Ca2+ permeability. |
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| 10712476 | Gibbs JW 3rd, Zhang YF, Shumate MD, Coulter DA: Regionally selective blockade of GABAergic inhibition by zinc in the thalamocortical system: functional significance. J Neurophysiol. 2000 Mar;83(3):1510-21. interacts with a variety of ionic conductances, including GABAR currents, (NMDA) receptor currents, and transient (A) currents. D-2-amino-5-phosphonovaleric acid and 4-aminopyridine blocked both s- and cTBCs in TC slices. |
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| 20336695 | Alonso E, Vale C, Sasaki M, Fuwa H, Konno Y, Perez S, Vieytes MR, Botana LM: oscillations induced by gambierol in cerebellar granule cells. J Cell Biochem. 2010 Mar 24. Gambierol-evoked [Ca (2+)] c oscillations were completely eliminated by the NMDA receptor antagonist APV and by riluzole and delayed by CNQX. In addition, the K (+) channel blocker 4-aminopyridine (4-AP)-evoked cytosolic oscillations in this neuronal system that were blocked by APV and delayed in the presence of CNQX. |
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| 19238257 | Brito VB, Rocha JB, Folmer V, Erthal F: Diphenyl diselenide and diphenyl ditelluride increase the latency for 4-aminopyridine-induced chemical seizure and prevent death in mice. Acta Biochim Pol. 2009;56(1):125-34. Epub 2009 Feb 23. It is possible that this effect results from modulation of the redox state of N-methyl-d-aspartate receptors and/or of Ca (2+) channel activity with subsequent alteration in neurotransmitter release. |
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| 15464283 | Bradford SE, Nadler JV: release from rat hippocampal synaptosomes. Neuroscience. 2004;128(4):751-65. In either case, they suggest is released mainly outside the presynaptic active zones and may therefore serve as the predominant agonist for extrasynaptic N-methyl-D-aspartate receptors. Both amino acids were released by 25 mM K (+), 300 microM 4-aminopyridine (4-AP) and 0.5 and 1 microM ionomycin in a predominantly Ca (2+)-dependent manner. |
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| 11877514 | Watabe AM, Carlisle HJ, O'Dell TJ: Postsynaptic induction and presynaptic expression of group 1 mGluR-dependent LTD in the hippocampal CA1 region. J Neurophysiol. 2002 Mar;87(3):1395-403. Consistent with this, induced a persistent depression of both AMPA and N-methyl-D-aspartate receptor-mediated components of excitatory postsynaptic currents in voltage-clamped pyramidal cells. Enhancing Ca (2+) influx by prolonging action potential duration with bath applications of the K (+) channel blocker 4-aminopyridine (4-AP) also strongly reduced the effects of in the presence of normal [Ca (2+)](o) (2 mM). |
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| 15829253 | Ogita K, Okuda H, Watanabe M, Nagashima R, Sugiyama C, Yoneda Y: In vivo treatment with the K+ channel blocker 4-aminopyridine protects against kainate-induced neuronal cell death through activation of NMDA receptors in murine hippocampus. Neuropharmacology. 2005 May;48(6):810-21. |
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| 16367773 | Ayala GX, Tapia R: Late N-methyl-D-aspartate receptor blockade rescues hippocampal neurons from excitotoxic stress and death after 4-aminopyridine-induced epilepsy. Eur J Neurosci. 2005 Dec;22(12):3067-76. |
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| 10570488 | Schoppa NE, Westbrook GL: Regulation of synaptic timing in the olfactory bulb by an A-type current. Nat Neurosci. 1999 Dec;2(12):1106-13. A transient A-type current (IA) specifically attenuated dendrodendritic inputs mediated by fast-acting AMPA receptors such that the excitation and subsequent inhibitory output of granule cells followed the prolonged kinetics of their NMDA receptors. |
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| 12213539 | Chen HH, Lee YF: Neonatal toluene exposure selectively alters sensitivity to different chemoconvulsant drugs in juvenile rats. Pharmacol Biochem Behav. 2002 Nov;73(4):921-7. Recent evidence indicates that this solvent is a noncompetitive inhibitor of (NMDA) receptors and enhances (A) (A)) receptor-mediated synaptic currents. Rats were administered (10 mg/ml), picrotoxin (2 mg/ml), pentylenetetrazol, (5 mg/ml) and 4-aminopyridine (4-AP; 2 mg/ml) via timed tail vein infusion on PN 34-36. |
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| 17005865 | Kalita K, Kharebava G, Zheng JJ, Hetman M: Role of megakaryoblastic acute leukemia-1 in ERK1/2-dependent stimulation of serum response factor-driven transcription by BDNF or increased synaptic activity. J Neurosci. 2006 Sep 27;26(39):10020-32. MKL1 regulation by synaptic activity was mediated through the NMDA receptor-activated ERK1/2. |
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| 19154779 | Borbely S, Dobo E, Czege D, Molnar E, Bakos M, Szucs B, Vincze A, Vilagi I, Mihaly A: Modification of ionotropic glutamate receptor-mediated processes in the rat hippocampus following repeated, brief seizures. Neuroscience. 2009 Mar 3;159(1):358-68. Epub 2008 Dec 27. Analysis of the population spikes revealed the reduced effectiveness of the AMPA receptor antagonist GYKI 52466, while the effect of the NMDA receptor antagonist d-(2R)-amino-5-phosphonovaleric acid was similar to controls. Daily repeated epileptic seizures were induced for 12 days by intraperitoneal administration of 4-aminopyridine (4-AP; 4.5 mg/kg) in adult Wistar rats. |
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| 11983316 | Yang L, Benardo LS: Laminar properties of 4-aminopyridine-induced synchronous network activities in rat neocortex. Neuroscience. 2002;111(2):303-13. The (A) receptor antagonist picrotoxin suppressed this spontaneous synchronous activity resistant to 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (a NMDA receptor antagonist) and 6-cyano-7-nitroquinoxaline-2,3-dione (a non-NMDA receptor antagonist), in superficial slices, leaving small, slow spontaneous events. |
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| 19939631 | Bertsche A, Bruehl C, Pietz J, Draguhn A: Region- and pattern-specific effects of uptake blockers on epileptiform activity in rat brain slices. Epilepsy Res. 2010 Feb;88(2-3):118-26. Epub 2009 Nov 24. Three different models were used to induce epileptiform discharges: (i) increasing NMDA receptor-mediated excitation by omitting Mg (2+)-ions; (ii) blocking channels by 4-aminopyridine; (iii) reducing (A) receptor-mediated inhibition by penicillin. |
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| 16122718 | Yang B, Leveck DE, Ferguson AV: Transient conductances protect nucleus tractus solitarius neurons from induced excitotoxic plateau depolarizations. Brain Res. 2005 Sep 14;1056(1):1-9. We identify two types of transient K (+) conductances (I (A) and I (D)), which contribute to the rapid repolarization of the membrane after a strong depolarization, and show that inhibition of these currents with 4-aminopyridine increases neuronal excitability after NMDA receptor activation such that DE cells now respond with LDPDs. |
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| 10805716 | Calcagnotto ME, Barbarosie M, Avoli M: Hippocampus-entorhinal cortex loop and seizure generation in the young rodent limbic system. J Neurophysiol. 2000 May;83(5):3183-7. Application of the convulsant 4-aminopyridine (4AP, 50 microM) to adult mouse combined hippocampus-entorhinal cortex (EC) slices induces interictal and ictal discharges originating from CA3 and EC respectively. In intact hippocampus-EC slices, ictal discharges were reduced by an N-methyl-D-aspartate receptor antagonist (n = 10). |
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| 19178556 | Panuccio G, Curia G, Colosimo A, Cruccu G, Avoli M: Epileptiform synchronization in the cingulate cortex. Epilepsia. 2009 Mar;50(3):521-36. Epub 2008 Oct 30. RESULTS: Bath-application of the convulsant 4-aminopyridine (4AP, 50 microM) induced both brief and prolonged periods of epileptiform synchronization resembling interictal- and ictal-like discharges, respectively. Interictal events could occur more frequently before the onset of ictal activity that was contributed by (NMDA) receptors. |
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| 14614906 | Murray KD, Isackson PJ, Jones EG: N-methyl-D-aspartate receptor dependent transcriptional regulation of two /calmodulin-dependent protein kinase type II isoforms in rodent cerebral cortex. Neuroscience. 2003;122(2):407-20. Organotypic cortical slice cultures treated with bicuculline and 4-aminopyridine to induce seizure activity also showed a downregulation of CaMKII-alpha mRNA and an upregulation of CaMKII-delta mRNA. |
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| 16181416 | Kopniczky Z, Dobo E, Borbely S, Vilagi I, Detari L, Krisztin-Peva B, Bagosi A, Molnar E, Mihaly A: Lateral entorhinal cortex lesions rearrange afferents, glutamate receptors, increase seizure latency and suppress seizure-induced c-fos expression in the hippocampus of adult rat. J Neurochem. 2005 Oct;95(1):111-24. Here we analysed the effects of one-sided lateral EC (LEC) and temporoammonic (alvear) path lesion on the development and properties of 4-aminopyridine-induced seizures. An increase in NR1 and NR2B (NMDA) receptor subunits and KA-2 kainate receptor subunit was identified in the deafferented layers of the hippocampus. |
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| 10589533 | Avoli M, Bernasconi A, Mattia D, Olivier A, Hwa GG: Epileptiform discharges in the human dysplastic neocortex: in vitro physiology and pharmacology. Ann Neurol. 1999 Dec;46(6):816-26. Ictal-like epileptiform discharges, along with isolated field potentials, were induced by bath application of 4-aminopyridine (50-100 microM). Ictal-like discharges were abolished by either or non-N-methyl-D-aspartate receptor antagonists. |
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