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1. |
Valproic Acid: Update on Its Mechanisms of Action |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 1-4
Daniel Johnston,
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摘要:
Valproic acid (VPA; 2‐propylpentanoic acid or dipropylacetic acid) was synthesized by Burton in 1882 and shown to have anticonvulsant properties by Meunier et al. in 1963. VPA was licensed for use as an anticonvulsant in the United States in 1978. It is used primarily for the treatment of generalized seizure
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb05630.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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2. |
Valproate: Recent Findings and Perspectives |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 5-9
M. Moire,
P. E. Keane,
J. C. Vernières,
J. Simiand,
R. Roncucci,
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摘要:
Valproate is a major antiepileptic drug that is now in worldwide clinical use. Nevertheless, the mechanism of action of valproate remains obscure. A number of recent articles have discussed this subject, and we ourselves have participated in a detailed review of the known actions of valproate (Chapman et al., 1982a). The object of this article is to present the most recent advances in our knowledge of valproate's actions, in particular, the pharmacological effects of some analogues and metabolites, the newest findings concerning the γ‐aminobutyric acid (GABA) hypothesis, and the possible involvement of valproate with ionic processes related to the intrinsic mechanisms of epilepsy at the cellular lev
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb05637.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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3. |
Neuropathological Findings in Primary Generalized Epilepsy: A Study of Eight Cases |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 8-21
H.‐J. Meencke,
D. Janz,
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摘要:
Summary:On neuropathological investigation of eight cases with primary generalized epilepsy, none showed elective parenchymal necrosis, which is regarded (qualitatively and topologically) as characteristic of epilepsy in classical neuropathology. In seven of the eight cases, however, marked microdysgenesis with varying regional distribution was found. These maturation disturbances are to be interpreted as pathological and refute the currently held view that there is no evidence of pathological brain damage in primary generalized epilepsy.RESUMENEn ninguna de las investigaciones neuropatológicas de los ocho casos estudiados con epilepsyía primaria se encontró necrosis paranquimatosa electiva, tal como se acepta como hal‐lazgo characterístico (cuantitativa y topográficamente) de epilepsyía en la neuropatología clásica. Sin embargo en siete de los ocho casos se encontró marcada microdisgenesia con distributeón regional variable. Estas alteraciones de la maduración se deben interpretar como hallazgos patológicos y se rechaza la opinión actual de que no existe evidencia de daño cerebral patológico en la epilepsyía generalizada primaria.ZUSAMMENFASSUNGBei neuropathologischen Untersuchungen von 8 Fällen mit primär generalisierter Epilepsie zeigte keiner eine elektive Parenchymnekrose, die (qualitativ und topologisch) von der klassischen Neuropathologie als charakteristisch für eine Epilepsie betrachtet wird. Bei 7 von 8 Fällen zeigte sich jedoch eine deutliche Mikrodysgenesie mit unterschiedlicher regionaler Verteilung. Diese Reifungsstörungen sind als pathologisch zu betrachten und widerlegen die gegenwärtig gültige Anschauung, daß as bei primär generalisierter Epilepsie keine Hinweise auf eine pathologisch anatomisch nachwe
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb04149.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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4. |
Variability in Level‐Dose Ratio of Valproate: Monotherapy Versus Polytherapy |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 10-13
Rene H. Levy,
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摘要:
One of the most useful pharmacokinetic parameters of a drug is the level‐dose ratio. This ratio originates from a relationship between the dosing rate (i.e., the daily dose) and the corresponding steady‐state plasma level. For most drugs that relationship is linear, indicating that changes in doses are associated with proportional changes in plasma levels. This proportionality between plasma level and dose is an expression of the fact that the clearance of the drug is constant. Valproic acid has been available in a number of countries for over a decade, and in spite of the large number of pharmacokinetic studies available in the literature, it is not possible, at the present time, to define a characteristic level‐dose ratio. This situation is a result of the fact that the clearance of valproate exhibits large interpatient variability. This article presents an analysis of the causes for the variability in valproate clearance. It is shown that when the determinants of valproate clearance are understood and taken into consideration, only a few factors are found to have a profound influence on it. Most important among these are age and polyth
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb05631.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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5. |
Valproic Acid and Metabolites: Pharmacological and Toxicological Studies |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 14-22
Heinz Nau,
Wolfgang Loscher,
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摘要:
Valproic acid (VPA) is a widely used anticonvulsant drug with a wide spectrum of activity, which is particularly well suited for the treatment of primary generalized seizures of the absence type.
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb05632.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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6. |
Epileptic Nystagmus Associated with Typical Absence Seizures |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 22-24
Kazuyoshi Watanabe,
Tamiko Negoro,
Akiko Matsumoto,
Kazuyo Inokuma,
Etsuko Takaesu,
Mitsuo Maehara,
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摘要:
Summary:A 10‐year‐old girl was reported who showed horizontal nystagmus in association with typical absence and 3‐cycles/s generalized, bisynchronous spike‐and‐wave discharges. In view of the general concept that epileptic nystagmus is a manifestation of partial seizures, the occurrence of such an association deserves documentation.RÉSUMÉLes auteurs rapportent le cas ď une fillette de 10 ans qui présentait un nystagmus horizontal au cours ď absences typiques avec décharges de P.O. à 3 c/s, généralisées, bisynchrones. Etant donné que le nystagmus épileptique est considére comme un symptôme de crise épileptique partielle, la survenue ď une telle association mérite ďétra documentée.RESUMENUna chica de 10 años presentó un nistagmo horizontal asociado con ausencias típicas y descargas de punta y onda bisíncromas, generalizadas de 3 c/s. En base al concepto general de que el nistagmo epiléptico es una manifestación de crisis parciales, la aparición de tal asociación merece documentatión.ZUSAMMENFASSUNGBericht über ein 10 Jahre altes Mädchen mit horizontalem Nystagmus in Verbindung mit typischen Absencen und generalisierten, seitengleichen 3/s spike wave Entladungen. Im Hinblick auf die allgemeine Annahme, daß den epileptogener Nystagmus ein Ausdruck von Partialanfällen ist, bedarf das Vork
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb04150.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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7. |
Open Trials with Valproate in Epilepsy |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 23-31
Olivier Dulac,
Michel Arthuis,
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摘要:
Valproic acid (VPA) was first synthesized in the United States (Burton, 1882) and was used worldwide for 80 years as an organic solvent. Its unexpected antiepileptic activity was discovered 20 years ago in Grenoble, France (Meunier et al., 1963; Carraz et al., 1964). The aim of this work is to report the progressive evolution of ideas and the clinical approach to the treatment of epilepsy with sodium valproate (Na VPA) and VPA, according to published open trials and to our own unpublished data.
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb05633.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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8. |
Seizures with Antidepressants: An In Vitro Technique to Assess Relative Risk |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 25-32
Daniel J. Luchins,
A. Paul Oliver,
Richard Jed Wyatt,
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摘要:
Summary:The relative potential of various antidepressants to induce seizures while being used at therapeutic doses was studied by examining their action on spike activity in perfused guinea pig hippocampal slices. Within the range of concentration studied, imipramine, amitriptyline, nortriptyline, maprotiline, and desipramine tended to increase spike activity in a descending order of effect. Doxepin and nomifensine increased spike activity at lower concentrations, but reduced it at higher concentrations. Protriptyline and trimipramine reduced spike activity with increasing concentrations, whereas mianserin and viloxazine had little effect at any concentration. These findings are discussed in light of previous clinical and laboratory reports, and the clinical implications of these findings are presented. Finally, results with the antidepressants are compared with those previously observed with neuroleptics. On the basis of this comparison and a review of clinical reports, the assumption that neuroleptics have greater epileptogenic potential than antidepressants is questioned.RESUMENLa posibilidad de que los antidepresivos produzcan ataques epilépticos en dosis terapeúticas ha sido estudiada examinando su acción sobre la actividad de las puntas en cortes perfundidos del hipocampo del cobaya. Dentro del rango de las concentra‐ciones estudiadas la imipramina, amitriptilina, nortriptilina, ma‐protilina y desipramina mostraron una tendencia a incrementar la actividad de las puntas en orden descendente de sus efectos. La doxepina y la nomifensina aumentaron la actividad de las puntas a concentraciones mas bajas pero la redujeron a más altas concentraciones. La protriptilina y latrimipraminadisminuyeron la actividad de las puntas en concentraciones incrementadas mientras que la mianserina y la viloxazina mostraron escasos efectos fuera cual fuese su concentrateón. Estos hallazgos se discuten teniendo en cuenta previos informes clínicos y de laboratorio y se presentan sus implicaciones clínicas. Finalmente, los resultados obtenidos con los antidepresivos se comparan con los observados previamente con los neurolépticos. Basándose en esta comparación y en la revisión de informes clinicos, se cuestiona la presunción de que los neurolépticos tienen mayor potencial epileptogénico que los antidepresivos.ZUSAMMENFASSUNGDie Gefahr, mit verschiedenen Antidepressiva in therapeutischer Dosierung Anfälle auszulösen, wurde an ihrer Wirkung auf die spike Aktivität von perfundierten Hippokampusschnitten des Meerschweinchens untersucht. Innerhalb der untersuchten Konzentrationen erhöhten Imipramin, Amitriptylin, Nortriptylin, Maprotilin und Desipramin die spike Aktivität in abnehmender Reihenfolge. Doxepin und Nomifensin erhöhten die spike Aktivität in niedrigen, verminderten sie in höheren Konzentrationen. Protriptylin und Trimipramin reduzierten die spike Aktivität mit zunehmenden Konzentrationen, während Mianserin und Viloxazin in keiner Konzentration wesentliche Wirkung zeigten. Diese Befunde werden im Lichte früherer klinischer und Laborergebnisse diskutiert und die klinischen Folgerungen dieser Befunde dargestellt. Schließlich werden die Befunde bei Antidepressiva verglichen mit den fruheren Beobachtungen an Neuroleptika. Nach diesem Vergleich und einem Überblick klinischer Arbeiten hierzu wird die Annahme in Frage gestellt das Neuroleptika ein großeres epileptogenes Potent
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb04151.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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9. |
Controlled and Comparative Trials of Valproate Performed in Europe and Asia |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 32-39
Lennart Gram,
Kirsten Drachmann Bentsen,
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摘要:
Scientifically sound investigation of new drug treatments necessitates the use of controlled designs, including random allocation and some kind of blind principle. Although this basic idea was conceived and applied, for the first time, more than a century ago, the trend of events has been tardy within all areas of medicine.
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb05634.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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10. |
Correlations Between Cerebellar Activity and Chronic Nontoxic Administration of Phenytoin in Rats |
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Epilepsia,
Volume 25,
Issue 1,
1984,
Page 33-39
O. Mameli,
E. Tolu,
F. Melis,
M. A. Caria,
G. Palmieri,
S. Piredda,
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摘要:
Summary:The effect of long‐term nontoxic treatment with phenytoin on the cerebellar Purkinje cell activity as determined by simultaneous monitoring of plasma and cerebellar levels of the drug has been studied in rats for the first time. The electrophysiological observations allowed the analysis of the spontaneous firing rate of the Purkinje cells and of the cerebellar field potentials generated by electrical stimulation of the ipsilateral radial nerve. The responses of single Purkinje cells to radial nerve stimulation were studied by constructing poststimulus time histograms and cumulative frequency distributions. The chronic treatment with phenytoin, which did not induce motor impairment or cerebellar symptoms, modified the firing rate of the Purkinje cells and the two modalities of Purkinje cell activation. In fact, phenytoin decreased significantly the spontaneous activity of the Purkinje cells and modified the strength of the mossy and climbing afferents.RESUMENPor primera vez se ha estudiado en ratas el efecto del tratamiento crónico, pero no tóxico, con fenitoina sobre la actividad de las cealulas de Purkinje durante la monitorización simultánea de niveles plasmáticos y cerebelosos de la droga. Las observaciones electrofisiológicas permitieron el análisis de la frecuencia de la actividad espontánea de las células de Purkinje y de los potenciales cerebelosos de campo, generados mediante estimulación eléctrica del nervio radial homolateral. Las respuestas de células de Purkinje aisladas a la estimulación del nervio radial han sido estudiadas mediante la construcción de histogramas de tiempo post‐estímulo y las distribuciones de frecuencias acumuladas. El tratamiento crónico COR fenitoína, que no había inducido alteraciones motoras o síntomas cerebelosos, modificó la frecuencia de la actividad de las células de Purkinje y las dos modalidades de activación de estas células. En realidad la fenitoína redujo significativamente la actividad espontánea de las células de Purkinje y modificó la fuerza de las aferentes musgosas y ascendentes.ZUSAMMENFASSUNGErstmalige Untersuchung der Wirkung einer chronischen, nicht toxischen Behandlung mit Phenytoin auf die Aktivität der cerebellären Purkinjezellen der Ratte bei gleichzeitiger Unter‐suchung der Medikamentenspiegel im Plasma und Cerebellum. Die elektrophysiologischen Beobachtungen erlauben eine Analyse der spontanen Entladungsrate der Purkinjezellen und der cerebellaren Feldpotential, die durch Elektrostimulation des ipsilateralen Radialisnewen gebildet werden. Die Antwort einzelner Purkinjezellen auf die Stimulation des Nervus radialis wurden durch Konstruktion von Zeit‐Histogrammen und kummulativen Frequenzverteilungen im Gefolge des Stimulus untersucht. Die chronische Behandlung mit Phenytoin, die keine motorische Beeinträchtigung Oder cerebelläre Symptome verursachte, modifizierte die Entladungsrate der Purkinjezellen und die zwei Modalitäten der Aktivierung von Purkinjezellen. Tatsächlich verminderte Phenytoin signifikant die spontane Aktivität der derkinjezellen und modifizierte die Stä
ISSN:0013-9580
DOI:10.1111/j.1528-1157.1984.tb04152.x
出版商:Blackwell Publishing Ltd
年代:1984
数据来源: WILEY
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