NG-Nitro-l-arginine impairs the anticonvulsive action of ethosuximide against pentylenetetrazol

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

doi:10.1016/s0014-2999(98)00927-3

Cited by 25 publications

(11 citation statements)

References 31 publications

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“…There is not much information available concerning NO involvement in convulsive mortality. By evaluating ED 50 in mice, Czuczwar et al 31 did not find a statistically significant influence of NNA on PTZ mortality. This is similar to our finding, even though mortality rate was decreased by 50%.…”

Section: Discussionmentioning

confidence: 93%

Nitric Oxide (NO) and Convulsions Induced by Pentylenetetrazol

Jelenković

Jovanović

Ninković

et al. 2002

Annals of the New York Academy of Sciences

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Data about the role of nitric oxide (NO) in epileptogenesis are contradictory. It is found to exert both proconvulsant and anticonvulsant effects. In an attempt to elucidate the role of NO in seizures, male Wistar rats were treated intraperitoneally by pentylenetetrazol (PTZ) (60, 80, and 100 mg/kg) and by a nitric oxide synthase antagonist, N-omega-nitro-L-arginine-methyl-ester (L-NAME) (10, 40, and 70 mg/kg), applied before PTZ. The time to onset and incidence of forelimb dystonia (FLD), generalized clonic convulsions (GCC), clonic-tonic convulsions (CTC), and mortality were recorded. The most successful convulsive response and mortality prevention were found in PTZ (80 mg/kg)-treated groups, where L-NAME (70 mg/kg) decreased the incidence by 29, 50, 67 (p = 0.052), and 50%, respectively, and significantly prolonged the time to onset, except that for mortality. Unexpectedly, L-NAME (40 mg/kg) increased incidence of GCC and mortality by 16%, similar to L-NAME (10 mg/kg) in PTZ (60 mg/kg)-treated groups, where GCC, CTC, and mortality increased by 14, 14, and 28%, respectively. Convulsive latency was prolonged in some PTZ (100 mg/kg) + L-NAME (40 and 70 mg/kg)-treated groups. In the experimental model and protocol used, it is concluded that (1) the effects of NO are L-NAME- and PTZ-dose dependent; (2) clonic-tonic convulsions are more strongly influenced by NO than limbic, probably because of PTZ limbic structure overstimulation; (3) L-NAME decreases the incidence of CTC and prolongs FLD, GCC, and CTC times to onset, indicating that NO acts as a proconvulsant; and (3) increased GCC, CTC, and mortality that suggests an anticonvulsant effect of NO needs further investigation.

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Section: Discussionmentioning

confidence: 93%

Nitric Oxide (NO) and Convulsions Induced by Pentylenetetrazol

Jelenković

Jovanović

Ninković

et al. 2002

Annals of the New York Academy of Sciences

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“…In contrast, L-arginine (500 mgkg) partially inhibited the impairment of the anticonvulsant activity of ethosuximide by NG-nitro-L-arginine methyl ester (40 mg/kg) in the pentylenetetrazol test, which could point to a NO-dependent mechanism (16).…”

Section: Discussionmentioning

confidence: 81%

“…The protective effects of 7-NI combined with PB or CBZ do not seem dependent on NO-mediated processes, since they were not reversed by L-arginine (500 mgkg). In our previous study, this dose was sufficient to prevent the N"-nitro-L-arginine-induced reduction in the anticonvulsant action of ethosuximide (16). Similarly, in the maximal electroshock model of experimental epilepsy, 7-NI enhanced (20) PB (30) PB (20) 7-NI (50) CBZ (20 7-NI, 7-nitroindazole; AED, antiepileptic drug; CBZ, carbamazepine; PB, phenobarbital.…”

Section: Discussionmentioning

confidence: 90%

“…Data exist on the influence of NOS inhibitors on the anticonvulsant action of conventional antiepileptic drugs (AEDs) against maximal electroshock-and pentylenetetrazol-induced seizures in mice (14)(15)(16). This study aims to evaluate the effects of 7-NI on the protection provided by conventional AEDs against amygdalakindled seizures in rats, the recommended model of complex partial seizures in humans (17).…”

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confidence: 99%

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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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“…In some cases, NOS inhibitors have potentiated the antiepileptic effect of these drugs (Baran et al, 1997;Borowicz et al, 1997Borowicz et al, , 2000Łuszczki et al, 2006, 2011De Sarro et al, 2000;Bahremand et al, 2010), while at other times they showed counteractive actions (Baran et al, 1997;Borowicz et al1998;Czuczwar et al, 1999;Lesani et al, 2010;Yahyavi-Firouz-Abadi et al, 2006) or even lack of effect (Borowicz et al, 1997(Borowicz et al, , 1998(Borowicz et al, , 2000Baran et al, 1997;Czuczwar et al, 1999;Łuszczki et al, 2006, 2011.…”

Section: Discussionmentioning

confidence: 99%