Levetiracetam in submaximal subcutaneous pentylentetrazol-induced seizures in rats

Coppola, Giangennaro; Arcieri, Salvatore; D’Aniello, Alfredo; Messana, Tullio; Verrotti, Alberto; Signoriello, Giuseppe; Pascotto, Antonio

doi:10.1016/j.seizure.2010.03.004

Cited by 24 publications

(14 citation statements)

References 20 publications

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“…Initially, different doses of these agents have been tested (in six to eight rats per dose) to determine the minimum dose that cause convulsions in all treated animals 51–55. This minimum dose was then used to screen potential AEDs.…”

Section: Methodsmentioning

confidence: 99%

“…Vehicle or tested compounds (VPA 100 or 300 mg/kg in PTZ and STR, respectively,39 PIT 10 mg/kg, or test compounds 1 – 6 at 10 mg/kg, all IP) were administered 30 minutes before PTZ or STR injection. All doses of test compounds were selected according to previously described methods 51–55. For the reference drug VPA, the dose (100 or 300 mg/kg, IP) that provided a full protection in the respective seizure model in rats without mortality was used.…”

Section: Methodsmentioning

confidence: 99%

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Anticonvulsant effects of isomeric nonimidazole histamine H<sub>3</sub> receptor antagonists

Sadek

Saad

Schwed

et al. 2016

DDDT

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Phenytoin (PHT), valproic acid, and modern antiepileptic drugs (AEDs), eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%–80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H3 receptors (H3Rs) for epilepsy might be a promising therapeutic approach. To determine the potential of H3Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the (S)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propanamide (1). In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R-enantiomer, namely, (R)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propaneamide (2) and analogs thereof, in maximum electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced convulsion models in rats having PHT and valproic acid (VPA) as reference AEDs. Unlike the S-enantiomer (1), the results show that animals pretreated intraperitoneally (ip) with the R-enantiomer 2 (10 mg/kg) were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier (R)-enantiomer (3), in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol, and its (S)-enantiomer (4) significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R)-enantiomer (3) in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and reversed when rats were pretreated with the selective H3R agonist R-(α)-methyl-histamine. Comparisons of the observed antagonistic in vitro affinities among the ligands 1–6 revealed profound stereoselectivity at human H3Rs with varying preferences for this receptor subtype. Moreover, the in vivo anticonvulsant effects observed in this study for ligands 1–6 showed stereoselectivity in different convulsion models in male adult rats.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Anticonvulsant effects of isomeric nonimidazole histamine H<sub>3</sub> receptor antagonists

Sadek

Saad

Schwed

et al. 2016

DDDT

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“…The neurophysiological and behavioral effects of the clinically used antidyskinetic drugs amanta- dine hydrochloride (an NMDA receptor antagonist, 50 and 50 mg/kg ip, t ϭ ϳ60 min), diazepam (a positive allosteric modulator at GABA A receptors, 5 mg/kg ip, t ϭ ϳ60 min), and levetiracetam (a presynaptic calcium channel inhibitor, 80 and 120 mg/kg ip, t ϭ ϳ30 min) were also evaluated. All drugs used in this study were obtained from Sigma-Aldrich, Sweden, and doses were chosen according to previously published studies (Coppola et al 2010;Kannari et al 2001;Peixoto et al 2005;Tronci et al 2014).…”

Section: Animalsmentioning

confidence: 99%

Systems-level neurophysiological state characteristics for drug evaluation in an animal model of levodopa-induced dyskinesia

Tamté

Brys

Richter

et al. 2016

Journal of Neurophysiology

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Disorders affecting the central nervous system have proven particularly hard to treat, and disappointingly few novel therapies have reached the clinics in recent decades. A better understanding of the physiological processes in the brain underlying various symptoms could therefore greatly improve the rate of progress in this field. We here show how systems-level descriptions of different brain states reliably can be obtained through a newly developed method based on large-scale recordings in distributed neural networks encompassing several different brain structures. Using this technology, we characterize the neurophysiological states associated with parkinsonism and levodopa-induced dyskinesia in a rodent model of Parkinson's disease together with pharmacological interventions aimed at reducing dyskinetic symptoms. Our results show that the obtained electrophysiological data add significant information to conventional behavioral evaluations and hereby elucidate the underlying effects of treatments in greater detail. Taken together, these results potentially open up for studies of neurophysiological mechanisms underlying symptoms in a wide range of neurological and psychiatric conditions that until now have been very hard to investigate in animal models of disease.

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“…administration at high doses (above 70 mg/kg) [6]. But it can also cause anxiety-like behavior at subconvulsive doses (from 15 to 30 mg/kg) [7].…”

Section: Introductionmentioning

confidence: 99%

Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ-Kindled Rats

Gáll

Koncz

Gáll

et al. 2017

Acta Medica Marisiensis

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Objective: This study evaluated the anticonvulsant action of lacosamide (LCS), a novel drug that was recently approved for the treatment of partial or secondarily generalized seizures, using an animal model of generalized epilepsy induced by repetitive pentylenetetrazole (PTZ) administration in rats. The main goal was to evaluate the behavioral pattern of lacosamide action by classifying seizures according to a modified Racine-scale. Furthermore, the reproducibility of the win-PTZ kindling model of epilepsy, a recently described variant of the standard PTZ-kindling model, was also assessed. Methods: Adult male Wistar rats (n=16) were divided into two groups and underwent the win-PTZkindling protocol in two independent trials. After finishing the kindling procedure, all animals, which presented stage 5 seizures were tested for the anticonvulsant action of lacosamide at three different doses (3, 10, and 30 mg/kg). Results: The maximal severity of seizures decreased and the latency to stage 3-5 seizures increased when the animals were treated with lacosamide at a single dose of 10 mg/kg compared to saline pretreatment (p < 0.05), both parameter reflecting an anticonvulsant action of the drug. Unfortunately, the number of stage 3-5 seizures also increased, but not significantly. The win-PTZ kindling model showed an adequate reproducibility between different trials, however, the number of fully kindled rats was lower than previously reported. Conclusions: Lacosamide showed a convincing anticonvulsant action in the win-PTZ kindling model of epilepsy by preventing the generalization of seizures. The win-PTZ kindling model was proved to be useful for studying epileptogenesis and the anticonvulsant action of drugs.

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Levetiracetam in submaximal subcutaneous pentylentetrazol-induced seizures in rats

Cited by 24 publications

References 20 publications

Anticonvulsant effects of isomeric nonimidazole histamine H<sub>3</sub> receptor antagonists

Anticonvulsant effects of isomeric nonimidazole histamine H<sub>3</sub> receptor antagonists

Systems-level neurophysiological state characteristics for drug evaluation in an animal model of levodopa-induced dyskinesia

Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ-Kindled Rats

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