NG-Nitro-L-arginine differentially affects glutamate-or kainateinduced seizures

Tutka, Piotr; Klonowski, Pawel; Dzieciuch, Jacek A; Kleinrok, Z; Czuczwar, Stanisław J.

doi:10.1097/00001756-199607080-00015

Cited by 48 publications

(16 citation statements)

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“…A similar result was reported by Penix et al (1994) who did not find any effect of NNA upon pentylenetetrazol-induced convulsions in rats. Also, no effect of NNA (up to 40mg/kg) was found upon the CDs0 values of pentylenetetrazol in mice (Tutka et al, 1996). Aminooxyacetic acid-induced seizures are thought to be mediated via disturbed transmission in the excitatory amino acid system .…”

Section: Discussionmentioning

confidence: 94%

“…In the same paradigm, L-arginine, potent NO donor, enhanced NMDA and kainate-induced convulsions (De Sarro et al, 1993). Systemic NNA was demonstrated to impair the convulsive activity of intracerebroventricular glutamate in mice (Tutka et al, 1996). However, there are numerous data suggesting proconvulsant properties of NO inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…However, the contribution of NO to the seizure events is still not clear. Available data show a lack of effect (Rondouin et al, 1992), as well as a decrease (De Sarro et al, 1991;Tutka et al, 1996) or an increase in seizure susceptibility (Przegaliriski et al, 1994;Rondouin et al, 1992;Starr and Starr, 1993) related to the inhibition of NO synthase. Therefore, we decided to study the influence of N<nitro-L-arginine (NNA), a powerful NO synthase inhibitor, upon various chemically and electrically induced seizures in mice.…”

Section: Introductionmentioning

confidence: 99%

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NG-nitro-L-arginine, a nitric oxide synthase inhibitor, and seizure susceptibility in four seizure models in mice

Drelewska

et al. 1996

J. Neural Transmission

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Nitric oxide may be involved in seizure phenomena even though data often seem to be contradictory. This prompted us to study the influence of nitric oxide upon electrically and chemically induced seizures. The effects of nitric oxide synthase inhibitor, NG-nitro-L-arginine (NNA), on pentylenetetrazol-, aminooxyacetic acid-, aminophylline-induced seizures or electroconvulsive shock were evaluated. NNA was applied at 1, 10 and 40 mg/ kg 0.5 and 2.0 h before chemical seizures and at 1 and 40 mg/kg 0.5 and 2.0 h prior to electroconvulsions. The nitric oxide synthase inhibitor (up to 40 mg/ kg) did not affect the susceptibility of mice to pentylenetetrazol, amino-oxyacetic acid or electroconvulsions. However, NNA significantly enhanced the convulsive properties of aminophylline when applied at 40 mg/kg, 0.5 h before the test. The CD50 value for aminophylline-induced clonus and tonus/ mortality was decreased from 233 to 191 and from 242 to 212 mg/kg, respectively. However, this pretreatment also led to a significant increase in the plasma levels of theophylline. Our results suggest that differential effects of NNA on chemically-induced convulsions might in some cases be associated with a pharmacokinetic interaction.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NG-nitro-L-arginine, a nitric oxide synthase inhibitor, and seizure susceptibility in four seizure models in mice

Drelewska

et al. 1996

J. Neural Transmission

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“…Although it has been suggested that NO participates in several neurodegenerative conditions, including epilepsy (24,25), its contribution to convulsant events is still unclear. Some available data related to NO synthase inhibition have shown a decreasing (23,26) or an increasing effect on seizure susceptibility (27,28).…”

Section: Discussionmentioning

confidence: 99%

Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

Reis

Doretto

Duarte

et al. 2003

Braz J Med Biol Res

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It was previously reported that systemic administration of dipyrone inhibited the tonic component of generalized tonic-clonic seizures in both the electroshock and the audiogenic seizure models. The aim of the present study was to investigate the mechanisms involved in the anticonvulsant action of dipyrone by assessing the role of nitric oxide and opioids in the electroshock (female 60-to 90-day-old Wistar rats, N = 5-11) and audiogenic seizure (female 60-to 90-day-old Wistar audiogenic rats, N = 5-11) models of epilepsy. Naloxone (5 mg/kg, sc) significantly reversed the anticonvulsant effect of dipyrone in rats submitted to the induction of audiogenic seizures (ANOVA/Bonferroni's test), suggesting the involvement of opioid peptides in this action. In the electroshock model no reversal of the anticonvulsant effect of dipyrone by naloxone (5 mg/kg, sc) was demonstrable. The acute (120 mg/kg, ip) and chronic (25 mg/kg, ip, twice a day/4 days) administration of L-NOARG did not reverse the anticonvulsant action of dipyrone in the audiogenic seizure model, suggesting that the nitric oxide pathway does not participate in such effect. Indomethacin (10, 20 and 30 mg/kg, ip) used for comparison had no anticonvulsant effect in the audiogenic seizure model. In conclusion, opioid peptides but not nitric oxide seem to be involved in the anticonvulsant action of dipyrone in audiogenic seizures. Correspondence

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“…Also, in (29)(30)(31). mice, NG-nitro-L-arginine methyl ester given at the same dose range behaved as an anticonvulsant in glutamateproduced seizures, and as a proconvulsant in kainateproduced ones (36). Finally, NOS inhibitors produced anticonvulsant or proconvulsant effects, depending on the dose administered (13).…”

Section: Discussionmentioning

confidence: 99%

7‐Nitroindazole Differentially Affects the Anticonvulsant Activity of Antiepileptic Drugs Against Amygdala‐Kindled Seizures in Rats

2000

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Summary:Purpose: The objective of this study was to evaluate the interaction of the preferential brain nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), with conventional antiepileptic drugs (AEDs) against amygdala-kindled seizures in rats. Methods: Experiments were performed on fully kindled rats. Adverse effects were evaluated with the rotorod test, which assesses motor coordination, and the passive-avoidance task, which assesses memory. Plasma levels of AEDs were measured by immunofluorescence. Results: 7-NI (up to 100 mg/kg) failed to modify seizure parameters. However, it reduced the severity and duration of kindled seizures when coadministered with otherwise ineffective doses of carbamazepine (CBZ) (10-20 mg/kg) or phenobarbital (PB) (20 mg/kg). Combinations of 7-NI with valproate (VPA), diphenylhydantoin (DPH), or clonazepam (CLO) were not protective. L-Arginine (500 mg/kg) did not reverse the seizure-suppressing interactions between 7-NI and the conventional AEDs. The combinations of 7-NI and CBZ or PB did not impair performance in the rotorod test. Coadministration of 7-NI with CBZ did not affect long-term memory, and 7-NI given with PB didn't affect the mnemonic effect of PB. Finally, 7-NI did not affect the free plasma levels of CBZ or PB. necessary to produce clonic convulsions in 50% of the a n i m a l s (3). In contrast, 7 -N I did not affect pentylenetetrazol-and kainate-induced seizures (3,4); but it did markedly suppress sound-induced seizures in DBA/2 mice as well as enoxacin-and pentylenetetrazolevoked seizures in mice. It also exerted protective activity in genetically epilepsy-prone rats (5-7), and it enhanced the severity of clonic convulsions and increased lethality produced by soman in rats (8).Researchers have proposed that NO plays an important role in mediating both the physiological and pathophysiological actions of excitatory amino acids. According to Reagan et al. (9), the stress-induced release of glutamate in the hippocampus was partially prevented by NOS inhibitors. It was also reported that kindled seizures caused a significant increase in NOS activity in the supraopticus nucleus (10) and the amygdala (1 1). Moreover, after hippocampal stimulation-evoked kindling, NOS messenger RNA decreased in the dentate granule cell layer and increased in the CA1 and CA3 pyramidal 1112

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NG-Nitro-L-arginine differentially affects glutamate-or kainateinduced seizures

Cited by 48 publications

References 0 publications

NG-nitro-L-arginine, a nitric oxide synthase inhibitor, and seizure susceptibility in four seizure models in mice

NG-nitro-L-arginine, a nitric oxide synthase inhibitor, and seizure susceptibility in four seizure models in mice

Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

7‐Nitroindazole Differentially Affects the Anticonvulsant Activity of Antiepileptic Drugs Against Amygdala‐Kindled Seizures in Rats

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