Effect of glutamate receptor antagonists on N-methyl-D-aspartate- and (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced convulsant effects in mice and rats

Bisaga, Adam; Krząścik, Paweł; Jankowska, Ewa A.; Palejko, W; Kostowski, Wojciech; Danysz, Wojciech

doi:10.1016/0014-2999(93)90244-c

Cited by 48 publications

(11 citation statements)

References 46 publications

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“…A variety of factors may change this profile of the drugs in vivo, particularly after systemic administration, making the interpretation of the mechanism of their effects difficult. Thus, GYKI 52466, which selectively blocked AMPA-activated currents in cultured hippocampal neurones (Donevan & Rogawski, 1993), has been reported to be a non-selective antagonist of both AMPA and NMDA-induced seizures when tested systemically (Bisaga et al, 1993). When tested on a small number of spinal motoneurones by either iontophoretic or intravenous administration in vivo, this compound did, however, appear selective for AMPA-evoked responses (Engberg et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

A comparison of intravenous NBQX and GYKI 53655 as AMPA antagonists in the rat spinal cord

Chizh

Cumberbatch

Headley

1994

British J Pharmacology

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1 The effects of intravenous administration of two z-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists were studied on responses of single neurones to iontophoretically applied excitatory amino acids. The tests were performed on spinal neurones in a-chloralose anaesthetized, spinalized rats. 2 Both the quinoxaline, NBQX (2-16mgkg-') and the 2,3-benzodiazepine, GYKI 53655 (2-8 mg kg-') dose-dependently decreased responses to AMPA. 3 Both compounds were short acting, with half-recovery times of 15 min for NBQX and 7 min for GYKI 53655. 4 The selectivity for responses to AMPA over those to N-methyl-D-aspartate (NMDA) was significantly poorer for systemic NBQX than for either systemic GYKI 53655 or iontophoretic NBQX, suggesting that systemic NBQX may be converted to a less selective metabolite. 5 GYKI 53655 is therefore likely to be a more valuable tool than NBQX for the study of AMPA receptor-mediated processes in vivo.

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Section: Discussionmentioning

confidence: 99%

A comparison of intravenous NBQX and GYKI 53655 as AMPA antagonists in the rat spinal cord

Chizh

Cumberbatch

Headley

1994

British J Pharmacology

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“…Nevertheless, NMDA receptor antagonists might be useful in the treatment of some types of seizures. For example, the well‐known NMDA receptor channel blocker memantine, which is approved for chronic clinical use in the treatment of Alzheimer's disease (Parsons et al, ; Lipton, ), exerted anticonvulsant effects in maximal electroshock seizures (MES; Chojnacka‐Wojcik et al, ; Urbanska et al, ; Parsons et al, ) and seizures induced by various chemoconvulsants (Meldrum et al, ; Bisaga et al, ; Parsons et al, ; Geter‐Douglass and Witkin, ; Lukomskaya et al, ; Mares and Mikulecka, ). However, high‐dose (20 mg/kg) memantine induced spontaneous motor seizures in amygdala‐kindled rats (Loscher and Honack, ).…”

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confidence: 99%

N‐methyl‐D‐aspartate receptor channel blockers prevent pentylenetetrazole‐induced convulsions and morphological changes in rat brain neurons

Zaitsev

Kim

Vasilev

et al. 2014

J of Neuroscience Research

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Alterations in inhibitory and excitatory neurotransmission play a central role in the etiology of epilepsy, with overstimulation of glutamate receptors influencing epileptic activity and corresponding neuronal damage. N-methyl-D-aspartate (NMDA) receptors, which belong to a class of ionotropic glutamate receptors, play a primary role in this process. This study compared the anticonvulsant properties of two NMDA receptor channel blockers, memantine and 1-phenylcyclohexylamine (IEM-1921), in a pentylenetetrazole (PTZ) model of seizures in rats and investigated their potencies in preventing PTZ-induced morphological changes in the brain. The anticonvulsant properties of IEM-1921 (5 mg/kg) were more pronounced than those of memantine at the same dose. IEM-1921 and memantine decreased the duration of convulsions by 82% and 37%, respectively. Both compounds were relatively effective at preventing the tonic component of seizures but not myoclonic seizures. Memantine significantly reduced the lethality caused by PTZ-induced seizures from 42% to 11%, and all animals pretreated with IEM-1921 survived. Morphological examination of the rat brain 24 hr after administration of PTZ revealed alterations in the morphology of 20-25% of neurons in the neocortex and the hippocampus, potentially induced by excessive glutamate. The expression of the excitatory amino acid transporter 1 protein was increased in the hippocampus of the PTZ-treated rats. However, dark neurons did not express caspase-3 and were immunopositive for the neuronal nuclear antigen protein, indicating that these neurons were alive. Both NMDA antagonists prevented neuronal abnormalities in the brain. These results suggest that NMDA receptor channel blockers might be considered possible neuroprotective agents for prolonged seizures or status epilepticus leading to neuronal damage.

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“…It is known that the rat hippocampus has a high density of glutamate receptors. It is widely accepted that different subtypes of glutamate receptors are involved in mechanisms of neuronal degeneration (43–45) and in epileptic activity (46,47). Thus we suggest that the effects of TsTx observed in the immediate period may be owing, at least in part, to the enhanced release of glutamate in the hippocampal pathways.…”

Section: Discussionmentioning

confidence: 99%

TsTx Toxin Isolated from Tityus serrulatus Scorpion Venom Induces Spontaneous Recurrent Seizures and Mossy Fiber Sprouting

2003

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Summary:Purpose: To characterize the long-term behavioral, electroencephalographic (EEG) and histopathologic features after a single TsTx microinjection into the hippocampus of rats.Methods: TsTx, 2 µg, or 1 µl of 0.1 M phosphate buffer was injected into the right dorsal hippocampus of the rat. EEG records and behavioral observations were made over a period of 10 h after injection. For a period of 4 months, the animals were observed for the occurrence of convulsive seizures. At the end of the experiment, the brains were processed by the neo-Timm and Nissl methods.Results: After intrahippocampal TsTx injection, three distinct phases were observed: (a) an immediate period that lasted 1 day, during which the motor and electrographic seizures characteristic of status epilepticus (SE) were seen; (b) a silent period (31-49 days), characterized by normal EEG and behavior;and (c) a period of spontaneous recurrent seizures (SRSs). The seizure frequency was one to two per week. Four months after TsTx injection, hippocampal neuronal loss and mossy fiber sprouting in the supragranular layer of the dentate gyrus were observed.Conclusions: The SRSs observed in this study may be associated with the TsTx-induced SE and brain damage. All animals injected with the toxin showed massive pyramidal neuronal loss in the dorsal hippocampus as well as intense gliosis and atrophy. Mossy fiber sprouting in the supragranular layer of the dentate gyrus was observed in those animals that had SRSs. The effects observed may be due, at least in part, to TsTx-enhanced release of glutamate in hippocampal pathways. Key Words: Scorpion toxin-Epilepsy-Hippocampal damage-Mossy fiber sprouting.A toxin isolated and sequenced from Tityus serrulatus scorpion venom in our laboratory showed full homology up to 26 amino acid residues with a toxin named IV-5 (or Ts IV) toxin by Possani et al. (1) and TsTx by Sampaio et al. (2). We had first named this toxin TS-8F (3), but later adopted TsTx to unify the nomenclature for this toxin. The effects of TsTx on guinea pig pancreatic secretion (1) and on glutamate release from brain structures (4,5), its antigenic properties (6), and the structural organization of scorpion toxin genes (7) have been studied. Sodium channels are the molecular targets for several groups of neurotoxins, which alter channel function by binding to specific receptor sites. Studies investigating the effect of different neurotoxins on voltage-dependent sodium channels have identified six different receptor sites. Receptor sites 3 and 4 of sodium channels are occupied by α-and β-scorpion toxins, respectively. TsTx has been shown to be of the α type (8). Scorpion α-toxins

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Effect of glutamate receptor antagonists on N-methyl-D-aspartate- and (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced convulsant effects in mice and rats

Cited by 48 publications

References 46 publications

A comparison of intravenous NBQX and GYKI 53655 as AMPA antagonists in the rat spinal cord

A comparison of intravenous NBQX and GYKI 53655 as AMPA antagonists in the rat spinal cord

N‐methyl‐D‐aspartate receptor channel blockers prevent pentylenetetrazole‐induced convulsions and morphological changes in rat brain neurons

TsTx Toxin Isolated from Tityus serrulatus Scorpion Venom Induces Spontaneous Recurrent Seizures and Mossy Fiber Sprouting

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