Effect of orally administered guanosine on seizures and death induced by glutamatergic agents

Lara, Diogo R.; Schmidt, André; Frizzo, Marcos Emílio dos Santos; Burgos, Javier S.; Ramı́rez, Galo; Souza, Diogo O.

doi:10.1016/s0006-8993(01)02734-2

Cited by 94 publications

(76 citation statements)

References 23 publications

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“…However, (i) intraperitoneal administration of Ado enhanced [309], (ii) an Ado receptor (A 1 and A 2 ) antagonist (theophylline) decreased [382] and (iii) activation of A 2A receptor triggered/maintained [302] the absence epileptic activity in WAG/Rij rats. In addition, the involvement of the adenosinergic system in the Guo-induced decrease in QA-induced seizure activity was excluded [62,89]. All of these data support the idea that the Guo-induced increase in Ado levels in the brain may not decrease epileptic activity, at least not in relation to absence epilepsy and QA-induced seizure activity.…”

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 90%

“…However, nonAdo nucleosides, such as Guo, Ino and Urd, may also decrease the EC level of the excitatory neurotransmitter glutamate and/or increase GABAergic inhibition [88][89][90] and participate in pathophysiological processes of epilepsy [58][59][60][61][62][63][64]. Consequently, not only Ado [27,33,[65][66][67] but also nonAdo nucleosides (e.g., Ino, Guo and Urd) and their derivatives may be potential drugs in the treatment of different types of epilepsies.…”

Section: Modulatory Role Of Nucleosides On Epileptic Activitymentioning

confidence: 99%

“…Guanosine also has antiseizure effects in rodent epilepsy models, most likely via Guo-induced modulation of the glutamatergic system [60][61][62][368][369][370][371]. Guo may bind to its putative (uncloned) G-protein-coupled receptors in the brain [50,51].…”

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 99%

“…Among their diverse neuromodulatory functions, nucleosides may have a role in the modulation of epileptic activity as well [27,33,[58][59][60][61][62][63][64][65][66][67][68][69]. Therefore, drugs or nucleoside derivatives effective on nucleoside uptake, nucleoside receptors or nucleoside metabolism may be useful for the treatment of different diseases in the CNS, such as epilepsy [31].…”

Section: Introductionmentioning

confidence: 99%

“…Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants have also been shown to be effective in treating epileptic seizures [27,32,65,67]. In addition, not only Ado but also non-Ado nucleosides (e.g., Guo, Ino and Urd) showed antiseizure/anticonvulsant activity in various epilepsy models and are potential candidates involved in Cyt: cytosine; DAG: diacylglycerol; ENT1/ENT2/ENT3/ENT4 transporters: ENT1/ENT2/ENT3/ENT4 subtype of equilibrative nucleoside transporters; "ei": equilibrative, NBTI (S-(4-nitrobenzyl)-6-thioinosine) insensitive type of ENTs; "es": equilibrative, NBTI sensitive type of ENTs; Gi, G0, Gs, Gq, Golf: G-proteins; GIRK: G-protein-dependent inwardly rectifying K + channels; Guo: guanosine; IP3: inositol 1,4,5-triphosphate; PLC: phospholipase C; Urd: uridine epilepsy [58,[60][61][62][63][64]70]. In this review, we summarize what is known about the nucleoside system in the brain in relation to its potential application against epileptic seizures.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

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Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 90%

Section: Modulatory Role Of Nucleosides On Epileptic Activitymentioning

confidence: 99%

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

View full text Add to dashboard Cite

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The modulatory effects of allopurinol on N‐methyl d‐aspartate receptors in the central nervous system

Paniz

Schmidt

Souza

2012

Cell Biochemistry & Function

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Effects of chronic administered guanosine on behavioral parameters and brain glutamate uptake in rats

Vinadé

Schmidt

Frizzo

et al. 2004

J of Neuroscience Research

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Oral and intraperitoneal administration of the nucleoside guanosine have been shown to prevent quinolinic acid- (QA) and alpha-dendrotoxin-induced seizures, impair memory, and impair anxiety in rats and mice. We investigated the effect of 2-weeks ad lib orally administered guanosine (0.5 mg/ml) on seizures induced by QA, inhibitory avoidance memory, and locomotor performance in rats. We also studied the mechanism of action of guanosine through the measurement of its concentration in the cerebrospinal fluid (CSF) and its effect on glutamate uptake in cortical slices of rats. QA produced seizures in 85% of rats, an effect partially prevented by guanosine (53% of seizures; P = 0.0208). Guanosine also impaired retention on the inhibitory avoidance task (P = 0.0278) and decreased locomotor activity on the open field test (P = 0.0101). The CSF guanosine concentration increased twofold in the treated group compared to that in the vehicle group (P = 0.0178). Additionally, QA promoted a 30% decrease in glutamate uptake as compared to that with intracerebroventricular saline administration, an effect prevented by guanosine in animals protected against QA-induced seizures. Altogether, these findings suggest a potential role of guanosine for treating diseases involving glutamatergic excitotoxicity such as epilepsy. These effects seem to be related to modulation of glutamate uptake.

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Effect of orally administered guanosine on seizures and death induced by glutamatergic agents

Cited by 94 publications

References 23 publications

The Antiepileptic Potential of Nucleosides

The Antiepileptic Potential of Nucleosides

The modulatory effects of allopurinol on N‐methyl d‐aspartate receptors in the central nervous system

Effects of chronic administered guanosine on behavioral parameters and brain glutamate uptake in rats

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