Convulsant effects of some xanthine derivatives in genetically epilepsy-prone rats

Sarro, Angela De; Grasso, Silvana; Zappalà, Maria; Nava, Felice; Sarro, G. De

doi:10.1007/pl00005027

Cited by 42 publications

(23 citation statements)

References 50 publications

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“…The oral subchronic treatment with APs for 5 days in SD rats did not induce the appearance of audiogenic seizures following auditory stimulation in comparison with the SD control group, as previously described (data not shown) [26,51,52]. In GEPR-0s, haloperidol, quetiapine, and aripiprazole did not induce any change compared with the control GEPR-0 group at all doses used, whereas clozapine, risperidone, and olanzapine were able to induce the appearance of clonic phase of the audiogenic seizures (score 2-3) at the highest doses used (Fig.…”

Section: Effects Of Daily Antipsychotic Treatment On Severity Of Audisupporting

confidence: 78%

“…Genetically epilepsy-prone rats (GEPRs) represent an established animal model to study the pathophysiology of seizures and to screen potential new antiepileptic drugs [24][25][26][27][28][29][30][31]. In this strain, epilepsy is genetically determined, even though the exact mechanisms underlying the development of the disorder remain incompletely understood [24,27].…”

Section: Introductionmentioning

confidence: 99%

“…A nonspecific propensity for generalized seizures, regardless of the eliciting stimuli, enhances the value of this strain of rats as a model in the study of gene-linked generalized epilepsy. GEPRs are a useful model of convulsive epilepsy; the rats exhibit generalized tonic-clonic seizures in response to certain stimuli (i.e., sound and hyperthermia), with a lower threshold and more intense seizure response to a given stimulus (i.e., electrical or chemical) than other strains [24,26,30,32]. Various neurotransmitters have been involved in the genesis of seizures in this animal model, and particular attention has been focused on both gamma-aminobutyric acid (GABA) and glutamate [24,33,34].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

et al. 2015

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Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

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Section: Effects Of Daily Antipsychotic Treatment On Severity Of Audisupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

et al. 2015

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“…Methylxanthines are used clinically as a diuretic, circulatory and respiratory stimulant, and treatment for headaches. The convulsive properties of methylxanthines have been well documented (14,15,29). Intoxication with caffeine and theophylline can lead to seizures at plasma concentrations Ͼ 100 M (30).…”

Section: Discussionmentioning

confidence: 99%

Glucose Transporter Type 1 Deficiency Syndrome (Glut1DS): Methylxanthines Potentiate GLUT1 Haploinsufficiency In Vitro

Yang

Klepper

et al. 2001

Pediatr Res

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“…sistemici su altri organi ed apparati (8)(9)(10)(11)(12)(13)(14). Questa selettività d'azione della doxofillina sarebbe dovuta alla scarsa affinità con i recettori A1 e A2 dell'adenosina ed all'assenza di interferenze con i canali del calcio e con i relativi flussi ionici (8,13,14).…”

Section: Analisi Economicaunclassified

Analisi costo/efficacia della doxofillina vs. teofillina nella terapia dell’asma cronica reversibile dell’adulto

Eandi

Berno

Pradelli

2002

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Doxofylline is a methyl-xanthine with bronchodilator activity which clinical efficacy in the treatment of asthma and COPD is equivalent to theophylline. Clinical trials prooved that while doxofylline is as effective as theophylline in the treatment of asthma, it is associated with lesser side effects. For our pharmacoeconomical evaluation, we employed the data of an international multi-centric study that compared the efficacy and tolerability of 12 weeks of treatment with either theophylline 250 mg tid, or doxofylline 400 mg tid, or placebo. The efficacy was evaluated with pulmonary function tests and by recording the number of asthma attacks and beta-2 agonist puffs: doxofylline 1200 mg/day and theophylline 750 mg/day resulted equally effective, but the former resulted better tolerated, as the adverse effects were lesser in number and severity. We performed a cost/effectiveness analysis in order to compare the two treatments, considering the perspective of the Italian health system (SSN) and of the Italian society. For the purposes of this analysis, the efficacy indices we considered were two: one simple, consisting in the number of avoided asthma attacks (AAA), and a more complex one, i.e. UATD (Utility Adjusted Therapy Days). For the construction of this index, we extracted the survival curve of the patients remaining in therapy; this curve showed that the cumulative number of therapy days is significantly greater in the doxofylline group, although the percentage of dropouts is similar at the end of the three months: this is due to the fact that the drop-outs in the theophylline group occur earlier after treatment start. The number of therapy days was then weighed for an utility index inversely proportional to the main daily number of avoided asthma attacks, thus obtaining the UATDs. The results of the cost/effectiveness analyses showed that doxofylline dominates theophylline treatment in asthma, as it is less expensive and more effective (in terms of AAAs and UATDs) for both considered decision-makers, i.e. Italian SSN and society. The consistency of these results was further confirmed by oneway sensitivity analyses.

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Convulsant effects of some xanthine derivatives in genetically epilepsy-prone rats

Cited by 42 publications

References 50 publications

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

Glucose Transporter Type 1 Deficiency Syndrome (Glut1DS): Methylxanthines Potentiate GLUT1 Haploinsufficiency In Vitro

Analisi costo/efficacia della doxofillina vs. teofillina nella terapia dell’asma cronica reversibile dell’adulto

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