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[PMID]:29037435
[Au] Autor:Barnes Heller H
[Ad] Endereço:Neurology/Neurosurgery, Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA. Electronic address: Heidi.barnesheller@wisc.edu.
[Ti] Título:Feline Epilepsy.
[So] Source:Vet Clin North Am Small Anim Pract;48(1):31-43, 2018 Jan.
[Is] ISSN:1878-1306
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Seizures occur commonly in cats and can be classified as idiopathic epilepsy, structural epilepsy, or reactive seizures. Pursuit of a diagnosis may include a complete blood count, serum biochemistry, brain MRI, and cerebrospinal fluid analysis as indicated. Antiepileptic drugs should be considered if a cat is having frequent seizures, or any 1 seizure longer than 5 minutes. Phenobarbital is often the drug of choice; however, levetiracetam may be more useful for certain types of epilepsy in cats. Long-term prognosis depends on the underlying diagnosis and response to therapy.
[Mh] Termos MeSH primário: Doenças do Gato
Epilepsia/veterinária
Convulsões/veterinária
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/uso terapêutico
Doenças do Gato/diagnóstico por imagem
Doenças do Gato/tratamento farmacológico
Doenças do Gato/etiologia
Gatos
Epilepsia/diagnóstico por imagem
Epilepsia/tratamento farmacológico
Epilepsia/etiologia
Fenobarbital/uso terapêutico
Piracetam/análogos & derivados
Piracetam/uso terapêutico
Prognóstico
Fatores de Risco
Convulsões/diagnóstico por imagem
Convulsões/tratamento farmacológico
Convulsões/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); 230447L0GL (etiracetam); YQE403BP4D (Phenobarbital); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE


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[PMID]:28460320
[Au] Autor:Redecker J; Wittstock M; Rösche J
[Ad] Endereço:Department of Neurology, University of Rostock, Germany.
[Ti] Título:The efficacy of different kinds of intravenously applied antiepileptic drugs in the treatment of status epilepticus. How can it be determined?
[So] Source:Epilepsy Behav;71(Pt A):35-38, 2017 Jun.
[Is] ISSN:1525-5069
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We explored the influence of four different efficacy criteria on the results of observational studies concerning the treatment of status epilepticus (SE) and its subtypes. We compared and contrasted the results of four different efficacy criteria for the effectiveness of phenytoin, valproate, levetiracetam, and lacosamide. Criterion 1=the last antiepileptic drug (AED) administered before SE termination. Criterion 2=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE and without changes in dosage or number of the co-medication. Criterion 3=the last drug introduced into the antiepileptic therapy or increased in dose within 24h before termination of the SE without changes in the co-medication. Criterion 4=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE even allowing changes in the co-medication. We used two-tailed χ -tests with the Yates adjustment for small samples to evaluate statistical differences between efficacy rates of different AEDs in the entire group and in subgroups of SE according to the second level of subdivisions in axis 1 and according to axis 2 of the new ILAE classification. A total of 145 treatment episodes in 124 patients (47 male, 77 female) were evaluated. There were 23 significant differences in efficacy according to the different criteria. Only criteria 1 and 3 led to significant results in our analysis. When incorporating theoretical considerations and the results of this study, criterion 3 seems to be the most appropriate measure for the evaluation of efficacy of an AED in the treatment of SE, because it seems to be more reasonable than criterion 1.
[Mh] Termos MeSH primário: Anticonvulsivantes/administração & dosagem
Estado Epiléptico/diagnóstico
Estado Epiléptico/tratamento farmacológico
[Mh] Termos MeSH secundário: Acetamidas/administração & dosagem
Administração Intravenosa
Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Comportamentos Relacionados com a Saúde
Seres Humanos
Masculino
Meia-Idade
Fenitoína/administração & dosagem
Piracetam/administração & dosagem
Piracetam/análogos & derivados
Estudos Retrospectivos
Resultado do Tratamento
Ácido Valproico/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Acetamides); 0 (Anticonvulsants); 230447L0GL (etiracetam); 563KS2PQY5 (lacosamide); 614OI1Z5WI (Valproic Acid); 6158TKW0C5 (Phenytoin); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28458437
[Au] Autor:Gupta M
[Ad] Endereço:Treatwell Skin Centre, Jammu, Jammu and Kashmir, India.
[Ti] Título:Levetiracetam-induced leukocytoclastic vasculitis.
[So] Source:Indian J Pharmacol;49(1):124-126, 2017 Jan-Feb.
[Is] ISSN:1998-3751
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:Drug-induced leukocytoclastic vasculitis is a small-vessel vasculitis that most commonly manifests with palpable purpuric lesions on gravity-dependent areas. Vasculitis occurs within weeks after initial administration of medication and demonstrates clearance upon withdrawal of medication. Levetiracetam, a pyrrolidone derivative, is used as an adjunctive therapy in patients with refractory focal epilepsy, myoclonic epilepsy, and primary generalized tonic-clonic seizures. We present a case of a 14-year-old female, who developed cutaneous small-vessel vasculitis within 8 days of initiation of levetiracetam. Vasculitis was successfully managed by discontinuation of medication and systemic corticosteroids. This adverse reaction, to the best of our knowledge, has not been previously reported in literature.
[Mh] Termos MeSH primário: Anticonvulsivantes/efeitos adversos
Piracetam/análogos & derivados
Vasculite Leucocitoclástica Cutânea/induzido quimicamente
[Mh] Termos MeSH secundário: Adolescente
Anticonvulsivantes/administração & dosagem
Epilepsia/tratamento farmacológico
Feminino
Glucocorticoides/uso terapêutico
Seres Humanos
Piracetam/administração & dosagem
Piracetam/efeitos adversos
Vasculite Leucocitoclástica Cutânea/tratamento farmacológico
Vasculite Leucocitoclástica Cutânea/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Glucocorticoids); 230447L0GL (etiracetam); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.4103/0253-7613.201020


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[PMID]:27778062
[Au] Autor:Tutka P; Kondrat-Wróbel MW; Zaluska K; Zólkowska D; Florek-Luszczki M; Luszczki JJ
[Ad] Endereço:Department of Pharmacology, University of Rzeszów, Al. Rejtana 16c, 35-959, Rzeszów, Poland. tutka@umlub.pl.
[Ti] Título:Cytisine inhibits the protective activity of various classical and novel antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice.
[So] Source:Psychopharmacology (Berl);234(2):281-291, 2017 Jan.
[Is] ISSN:1432-2072
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cytisine (CYT) is a partial agonist of brain α4ß2 nicotinic acetylcholine receptors widely used in Central/Eastern Europe for smoking cessation. OBJECTIVES: This study evaluated the effect of CYT on the ability of classical and novel antiepileptic drugs to prevent seizures evoked by the 6-Hz test, a model of psychomotor seizures in mice thought as a model of drug-resistant seizures. RESULTS: CYT administered intraperitoneally (i.p.) in a dose of 2 mg kg significantly inhibited the anticonvulsant activity of lacosamide, levetiracetam, and pregabalin, increasing their median effective doses 50 (ED ) values from 6.88 to 10.52 mg kg (P < 0.05) for lacosamide, from 22.08 to 38.26 mg kg (P < 0.05) for levetiracetam, and from 40.48 to 64.61 mg kg (P < 0.01) for pregabalin, respectively. There were no significant changes in total brain concentrations of lacosamide, levetiracetam, and pregabalin following CYT i.p. administration. CYT administered in a dose of 2 mg kg failed to change the protective action of clobazam, clonazepam, phenobarbital, tiagabine, and valproate in the 6-Hz test. Neither CYT (2 mg kg ) alone nor its combination with the anticonvulsant drugs (at their ED values from the 6-Hz test) affected motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; and grip strength and passive avoidance tests, respectively. CONCLUSION: CYT-evoked alterations in the protection provided by some antiepileptic drugs against seizures can be of serious concern for epileptic smokers, who might demonstrate therapeutic failure to lacosamide, levetiracetam, and pregabalin, resulting in possible breakthrough seizure attacks.
[Mh] Termos MeSH primário: Alcaloides/toxicidade
Anticonvulsivantes/uso terapêutico
Eletrochoque/efeitos adversos
Agonistas Nicotínicos/toxicidade
Convulsões/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/farmacologia
Azocinas/toxicidade
Relação Dose-Resposta a Droga
Masculino
Memória de Longo Prazo/efeitos dos fármacos
Memória de Longo Prazo/fisiologia
Camundongos
Fenobarbital/antagonistas & inibidores
Fenobarbital/farmacologia
Fenobarbital/uso terapêutico
Piracetam/análogos & derivados
Piracetam/antagonistas & inibidores
Piracetam/farmacologia
Piracetam/uso terapêutico
Quinolizinas/toxicidade
Convulsões/etiologia
Convulsões/psicologia
Ácido Valproico/antagonistas & inibidores
Ácido Valproico/farmacologia
Ácido Valproico/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Anticonvulsants); 0 (Azocines); 0 (Nicotinic Agonists); 0 (Quinolizines); 230447L0GL (etiracetam); 53S5U404NU (cytisine); 614OI1Z5WI (Valproic Acid); YQE403BP4D (Phenobarbital); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171205
[Lr] Data última revisão:
171205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1007/s00213-016-4461-0


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[PMID]:28859122
[Au] Autor:Luszczki JJ; Patrzylas P; Zagaja M; Andres-Mach M; Zaluska K; Kondrat-Wrobel MW; Szpringer M; Chmielewski J; Florek-Luszczki M
[Ad] Endereço:Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
[Ti] Título:Effects of arachidonyl-2'-chloroethylamide (ACEA) on the protective action of various antiepileptic drugs in the 6-Hz corneal stimulation model in mice.
[So] Source:PLoS One;12(8):e0183873, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Accumulating evidence indicates that cannabinoid CB1 receptor ligands play a pivotal role in seizures, not only in preclinical studies on animals, but also in clinical settings. This study was aimed at characterizing the influence of arachidonyl-2'-chloroethylamide (ACEA-a selective cannabinoid CB1 receptor agonist) co-administered with phenylmethylsulfonyl fluoride (PMSF) on the anticonvulsant potency of various antiepileptic drugs (clobazam, lacosamide, levetiracetam, phenobarbital, tiagabine and valproate) in the 6-Hz corneal stimulation model. Psychomotor seizures in male albino Swiss mice were evoked by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via corneal electrodes. Potential adverse effects produced by the antiepileptic drugs in combination with ACEA+PMSF were assessed using the chimney test (motor performance), passive avoidance task (remembering and acquisition of learning), and grip-strength test (muscular strength). Brain concentrations of antiepileptic drugs were measured by HPLC to exclude any pharmacokinetic contribution to the observed effect. ACEA (5 mg/kg, i.p.) + PMSF (30 mg/kg, i.p.) significantly potentiated the anticonvulsant potency of levetiracetam (P<0.05), but not that of clobazam, lacosamide, phenobarbital, tiagabine or valproate in the 6-Hz corneal stimulation model. Moreover, ACEA+PMSF did not significantly affect total brain concentrations of levetiracetam in mice. No behavioral side effects were observed in animals receiving combinations of the studied antiepileptic drugs with ACEA+PMSF. In conclusion, the combined administration of ACEA+PMSF with levetiracetam is associated with beneficial anticonvulsant pharmacodynamic interaction in the 6-Hz corneal stimulation model. The selective activation of cannabinoid CB1 receptor-mediated neurotransmission in the brain may enhance levetiracetam-related suppression of seizures in epilepsy patients, contributing to the efficacious treatment of epilepsy in future.
[Mh] Termos MeSH primário: Anticonvulsivantes/farmacologia
Ácidos Araquidônicos/farmacologia
Epilepsia Parcial Complexa/tratamento farmacológico
Fluoreto de Fenilmetilsulfonil/farmacologia
Piracetam/análogos & derivados
Receptor CB1 de Canabinoide/agonistas
[Mh] Termos MeSH secundário: Acetamidas/farmacologia
Animais
Aprendizagem da Esquiva/efeitos dos fármacos
Benzodiazepinas/farmacologia
Córnea
Modelos Animais de Doenças
Sinergismo Farmacológico
Quimioterapia Combinada
Eletrochoque/métodos
Epilepsia Parcial Complexa/metabolismo
Epilepsia Parcial Complexa/fisiopatologia
Masculino
Camundongos
Força Muscular/efeitos dos fármacos
Ácidos Nipecóticos/farmacologia
Fenobarbital/farmacologia
Piracetam/farmacologia
Desempenho Psicomotor/efeitos dos fármacos
Ácido Valproico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetamides); 0 (Anticonvulsants); 0 (Arachidonic Acids); 0 (Nipecotic Acids); 0 (Receptor, Cannabinoid, CB1); 0 (arachidonyl-2-chloroethylamide); 12794-10-4 (Benzodiazepines); 230447L0GL (etiracetam); 2MRO291B4U (clobazam); 563KS2PQY5 (lacosamide); 57KD15003I (Phenylmethylsulfonyl Fluoride); 614OI1Z5WI (Valproic Acid); YQE403BP4D (Phenobarbital); Z80I64HMNP (tiagabine); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183873


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[PMID]:28847876
[Au] Autor:Kelly D; Raimondi F; Shihab N
[Ad] Endereço:Department of Internal Medicine, Southern Counties Veterinary Specialists LLP, Ringwood, UK.
[Ti] Título:Levetiracetam monotherapy for treatment of structural epilepsy in dogs: 19 cases (2010-2015).
[So] Source:Vet Rec;181(15):401, 2017 Oct 14.
[Is] ISSN:2042-7670
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To evaluate the efficacy and tolerability of levetiracetam monotherapy in dogs with structural epilepsy. Retrospective case series. Nineteen client-owned dogs with structural epilepsy. Seizure frequencies after initiation of treatment were used to evaluate the efficacy of levetiracetam monotherapy. Seizure control was considered good if no seizures occurred within three months of starting treatment or poor if seizures returned within one month of starting treatment. Tolerability was evaluated by considering the occurrence and severity of any reported side effects. Ten of the 19 dogs were considered to have a good response to treatment with 7 achieving complete seizure freedom. Nine dogs were considered to have poor response to treatment. There was a statistically significant reduction in the percentage of patients experiencing cluster seizures from 68.4% to 15.8% (p=0.002). Side effects were noted in 8 of the 19 dogs but were considered mild in all cases. Follow-up times ranged from 12 days to 426 days. When used in conjunction with other appropriate therapies, levetiracetam may be an efficacious option for monotherapy in dogs with structural epilepsy. Its tolerability makes it a suitable option for use in a wide variety of patients.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Doenças do Cão/tratamento farmacológico
Epilepsia/veterinária
Piracetam/análogos & derivados
Convulsões/veterinária
[Mh] Termos MeSH secundário: Animais
Cães
Epilepsia/tratamento farmacológico
Seguimentos
Piracetam/uso terapêutico
Estudos Retrospectivos
Convulsões/prevenção & controle
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 230447L0GL (etiracetam); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE
[do] DOI:10.1136/vr.104190


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[PMID]:28833036
[Au] Autor:Nemes AD; O'Dwyer R; Najm IM; Ying Z; Gonzalez-Martinez J; Alexopoulos AV
[Ad] Endereço:Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, U.S.A.
[Ti] Título:Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia.
[So] Source:Epilepsia;58(10):1755-1761, 2017 Oct.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. METHODS: Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA ) antagonist used to provoke generalized seizures as a "second hit." RESULTS: LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. SIGNIFICANCE: Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology.
[Mh] Termos MeSH primário: Acetamidas/farmacologia
Anticonvulsivantes/farmacologia
Malformações do Desenvolvimento Cortical/fisiopatologia
Convulsões/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Eletroencefalografia
Feminino
Antagonistas GABAérgicos/toxicidade
Malformações do Desenvolvimento Cortical/etiologia
Pentilenotetrazol/toxicidade
Piracetam/análogos & derivados
Piracetam/farmacologia
Gravidez
Efeitos Tardios da Exposição Pré-Natal
Exposição à Radiação/efeitos adversos
Ratos
Ratos Sprague-Dawley
Convulsões/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetamides); 0 (Anticonvulsants); 0 (GABA Antagonists); 230447L0GL (etiracetam); 563KS2PQY5 (lacosamide); WM5Z385K7T (Pentylenetetrazole); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13856


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[PMID]:28829199
[Au] Autor:Russo E; Citraro R; Mula M
[Ad] Endereço:a Science of Health Department, School of Medicine and Surgery , University of Catanzaro , Catanzaro , Italy.
[Ti] Título:The preclinical discovery and development of brivaracetam for the treatment of focal epilepsy.
[So] Source:Expert Opin Drug Discov;12(11):1169-1178, 2017 Nov.
[Is] ISSN:1746-045X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Brivaracetam (BRV) is a new AED currently licensed for the adjunctive treatment of adult patients with focal epilepsies. It is a ligand of the ubiquitous synaptic vesicle glycoprotein 2A (SV2A). Areas covered: This paper covers the preclinical and subsequent clinical development of BRV focusing on the discovery of the SV2A protein as the main target for levetiracetam (LEV) and the main similarities and differences between LEV and BRV in terms of pharmacodynamic and pharmacokinetic properties. Phase II and Phase III studies are also presented and data from post-marketing phase IV studies are discussed. Expert opinion: The preclinical development of BRV is quite unique and has raised several doubts on current methodologies adopted for AED development, reinforcing the need for new approaches. The preclinical and clinical profile suggest that BRV is potentially an ideal compound in the emergency setting given the rapid onset of action associated with being water soluble and, therefore, available in intravenous formulation. In addition, data from Phase III studies have already suggested that BRV may be effective not only in focal epilepsies but also in generalised syndromes. Further data from special populations such as children and women of child bearing age are urgently needed.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Epilepsias Parciais/tratamento farmacológico
Pirrolidinonas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Animais
Anticonvulsivantes/farmacocinética
Anticonvulsivantes/farmacologia
Descoberta de Drogas/métodos
Epilepsias Parciais/fisiopatologia
Seres Humanos
Ligantes
Glicoproteínas de Membrana/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Piracetam/análogos & derivados
Piracetam/farmacocinética
Piracetam/farmacologia
Piracetam/uso terapêutico
Pirrolidinonas/farmacocinética
Pirrolidinonas/farmacologia
Solubilidade
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Ligands); 0 (Membrane Glycoproteins); 0 (Nerve Tissue Proteins); 0 (Pyrrolidinones); 148845-93-6 (SV2A protein, human); 230447L0GL (etiracetam); U863JGG2IA (brivaracetam); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1080/17460441.2017.1366985


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[PMID]:28766701
[Au] Autor:Puligheddu M; Melis M; Pillolla G; Milioli G; Parrino L; Terzano GM; Aroni S; Sagheddu C; Marrosu F; Pistis M; Muntoni AL
[Ad] Endereço:Sleep Disorder Research Center, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
[Ti] Título:Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy.
[So] Source:Epilepsia;58(10):1762-1770, 2017 Oct.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or ß2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of ß2-containing nAChR. To test clinical efficacy of adjunctive therapy with fenofibrate in pharmacoresistant ADNFLE\NFLE patients, we first demonstrated the effectiveness of fenofibrate in a mutated mouse model displaying both disease genotype and phenotype. METHODS: We first tested the efficacy of fenofibrate in transgenic mice carrying the mutation in the α4-nAChR subunit (Chrna4S252F) homologous to that found in humans. Subsequently, an add-on protocol was implemented in a clinical setting and fenofibrate was administered to pharmacoresistant NFLE patients. RESULTS: Here, we show that a chronic fenofibrate diet markedly reduced the frequency of large inhibitory postsynaptic currents (IPSCs) recorded from cortical pyramidal neurons in Chrna4S252F mice, and prevented nicotine-induced increase of IPSC frequency. Moreover, fenofibrate abolished differences between genotypes in the frequency of sleep-related movements observed under basal conditions. Patients affected by NFLE, nonresponders to traditional therapy, by means of adjunctive therapy with fenofibrate displayed a reduction of seizure frequency. Furthermore, digital video-polysomnographic recordings acquired in NFLE subjects after 6 months of adjunctive fenofibrate substantiated the significant effects on control of motor-behavioral seizures. SIGNIFICANCE: Our preclinical and clinical studies suggest PPARα as a novel disease-modifying target for antiepileptic drugs due to its ability to regulate dysfunctional nAChRs.
[Mh] Termos MeSH primário: Anticonvulsivantes/farmacologia
Epilepsia Resistente a Medicamentos/tratamento farmacológico
Epilepsia do Lobo Frontal/tratamento farmacológico
Fenofibrato/uso terapêutico
PPAR alfa/agonistas
[Mh] Termos MeSH secundário: Adulto
Animais
Benzodiazepinas/uso terapêutico
Carbamazepina/análogos & derivados
Carbamazepina/uso terapêutico
Modelos Animais de Doenças
Epilepsia Resistente a Medicamentos/genética
Quimioterapia Combinada
Eletroencefalografia
Epilepsia do Lobo Frontal/genética
Feminino
Fenofibrato/farmacologia
Seres Humanos
Masculino
Camundongos
Camundongos Transgênicos
Meia-Idade
Mutação
Piracetam/análogos & derivados
Piracetam/uso terapêutico
Polissonografia
Receptores Nicotínicos/genética
Triazinas/uso terapêutico
Ácido Valproico/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (PPAR alpha); 0 (Receptors, Nicotinic); 0 (Triazines); 0 (nicotinic acetylcholine receptor alpha4 subunit); 12794-10-4 (Benzodiazepines); 230447L0GL (etiracetam); 2MRO291B4U (clobazam); 33CM23913M (Carbamazepine); 614OI1Z5WI (Valproic Acid); U202363UOS (Fenofibrate); U3H27498KS (lamotrigine); VZI5B1W380 (oxcarbazepine); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13863


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[PMID]:28731266
[Au] Autor:Schoenberg MR; Rum RS; Osborn KE; Werz MA
[Ad] Endereço:Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, U.S.A.
[Ti] Título:A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults.
[So] Source:Epilepsia;58(9):1566-1574, 2017 Sep.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults. METHODS: Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65-80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65-80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale). RESULTS: Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5). SIGNIFICANCE: LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance.
[Mh] Termos MeSH primário: Afeto/efeitos dos fármacos
Cognição/efeitos dos fármacos
Nootrópicos/farmacologia
Piracetam/análogos & derivados
Equilíbrio Postural/efeitos dos fármacos
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Estudos Cross-Over
Método Duplo-Cego
Esquema de Medicação
Feminino
Seres Humanos
Masculino
Piracetam/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Nootropic Agents); 230447L0GL (etiracetam); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13849



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