<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Nitric oxide (NO) participates in processes such as endothelium-dependent vasodilation and neurotransmission/neuromodulation. The role of NO in epilepsy is controversial, attributing it to anticonvulsant but also proconvulsant properties. Clarification of this dual effect of NO might lead to the development of new antiepileptic drugs. Previous results in our laboratory indicated that this contradictory role of NO in seizures could depend on the nitric oxide synthase (NOS) isoform involved, which could play opposite roles in epileptogenesis, one of them being proconvulsant but the other anticonvulsant. The effect of convulsant drugs on neuronal NO (nNO) and endothelial NO (eNO) levels was investigated. Considering the distribution of neuronal and endothelial NOS in neurons and astrocytes, resp., primary cultures of neurons and astrocytes were used as a study model. The effects of convulsant drugs pentylenetetrazole, thiosemicarbazide, 4-aminopyridine and bicuculline on NO levels were studied, using a spectrophotometric method. Their effects on NO levels in neurons and astrocytes depend on the concentration and time of treatment. These convulsant drugs caused an increase in nNO, but a decrease in eNO was proportional to the duration of treatment in both cases. Apparently, nNO possesses convulsant properties mediated by its effect on the glutamatergic and GABAergic systems, probably through GABA<sub>A</sub> receptors. Anticonvulsant properties of eNO may be the consequence of its effect on endothelial vasodilation and its capability to induce angiogenesis. Described effects last as seizures do. Considering the limitations of these kinds of studies and the unexplored influence of inducible NO, further investigations are required.</p>
</abstract>

Nitric oxide (NO) participates in processes such as endothelium-dependent vasodilation and neurotransmission/neuromodulation. The role of NO in epilepsy is controversial, attributing it to anticonvulsant but also proconvulsant properties. Clarification of this dual effect of NO might lead to the development of new antiepileptic drugs. Previous results in our laboratory indicated that this contradictory role of NO in seizures could depend on the nitric oxide synthase (NOS) isoform involved, which could play opposite roles in epileptogenesis, one of them being proconvulsant but the other anticonvulsant. The effect of convulsant drugs on neuronal NO (nNO) and endothelial NO (eNO) levels was investigated. Considering the distribution of neuronal and endothelial NOS in neurons and astrocytes, resp., primary cultures of neurons and astrocytes were used as a study model. The effects of convulsant drugs pentylenetetrazole, thiosemicarbazide, 4-aminopyridine and bicuculline on NO levels were studied, using a spectrophotometric method. Their effects on NO levels in neurons and astrocytes depend on the concentration and time of treatment. These convulsant drugs caused an increase in nNO, but a decrease in eNO was proportional to the duration of treatment in both cases. Apparently, nNO possesses convulsant properties mediated by its effect on the glutamatergic and GABAergic systems, probably through GABAA receptors. Anticonvulsant properties of eNO may be the consequence of its effect on endothelial vasodilation and its capability to induce angiogenesis. Described effects last as seizures do. Considering the limitations of these kinds of studies and the unexplored influence of inducible NO, further investigations are required.

The opposite effect of convulsant drugs on neuronal and endothelial nitric oxide synthase – A possible explanation for the dual proconvulsive/anticonvulsive action of nitric oxide

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Nitric oxide (NO) participates in processes such as endothelium-dependent vasodilation and neurotransmission/neuromodulation. The role of NO in epilepsy is...

The opposite effect of convulsant drugs on neuronal and endothelial nitric oxide synthase – A possible explanation for the dual proconvulsive/anticonvulsive action of nitric oxide

Published Online: Jan 24, 2023

Page range: 59 - 74

Accepted: Aug 21, 2022

DOI: https://doi.org/10.2478/acph-2023-0004

Keywords
epilepsy, nitric oxide, seizures, endothelial nitric oxide, neuronal nitric oxide

© 2023 Lourdes A. Vega Rasgado et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

The opposite effect of convulsant drugs on neuronal and endothelial nitric oxide synthase – A possible explanation for the dual proconvulsive/anticonvulsive action of nitric oxide

Published Online: Jan 24, 2023

Page range: 59 - 74

Accepted: Aug 21, 2022

DOI: https://doi.org/10.2478/acph-2023-0004

Keywordsepilepsy, nitric oxide, seizures, endothelial nitric oxide, neuronal nitric oxide

© 2023 Lourdes A. Vega Rasgado et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
epilepsy, nitric oxide, seizures, endothelial nitric oxide, neuronal nitric oxide