FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2137202579> ?p ?o ?g. }

• W2137202579 endingPage "270" @default.
• W2137202579 startingPage "241" @default.
• W2137202579 abstract "ABSTRACT- Gamma-aminobutyric acid (GABA) is the most important inhibitory transmitter, quantitatively, in the CNS. Evidence exists that decreased GABAergic neurotransmission may play a role in some forms of epilepsy. Consequently, manipulating the GABA system may be a therapeutic possibility in the treatment of this disease. Inhibition of the major GABA degrading enzyme, GABA-transaminase (GABA-T), seems to be the most promising approach. Currently, 2 antiepileptic drugs, valproate (VPA) and vigabatrin, gamma-vinyl GABA (GVG), are available, which are supposed to inhibit the degradation of GABA. Both drugs cause an increase in the total concentration of GABA in the brain, but to a different extent. VPA produces a moderate elevation, which seems to be the result of a marked increase in the transmitter-related GABA pool, while the pronounced elevation in GABA concentration observed during treatment with GVG seems to be caused mainly by an increase in the non-transmitter-related (glial) GABA pool. In order to investigate this apparently differential influence of VPA and GVG on the GABA system, a number of studies were undertaken in selectively cultured astrocytes and neurons from mice. For both drugs neuronal GABA-T proved far more sensitive with regard to inhibition than glial GABA-T. In order to obtain a more direct measure of a potential GABAergic mechanism of action of VPA and GVG, synaptic release of endogenous GABA was determined after culturing neurons in the presence of clinically relevant concentrations of the drugs. GVG caused a significant increase in GABA release, even at concentrations as low as 25 μM. For VPA only the highest of the investigated concentrations (300 μM) augmented GABA release. It is concluded that the antiepileptic effect of GVG seems to be caused by a direct GABAergic mechanism of action. For VPA an influence on the GABA system may play a role in the antiepileptic effect of the drug. However, the lack of definite data on human brain levels of VPA after chronic treatment, combined with evidence that VPA exhibits a number of other effects that may be relevant for its antiepileptic properties, makes the interpretation of a GABAergic mechanism of action difficult. Controlled clinical trials have been increasingly applied within all areas of medicine. In 1982 a survey of the literature identified 29 studies of antiepileptic drugs, where the design involved randomization, the double-blind principle and a statistical analysis of the results. A cross-sectional analysis of these trials demonstrated a number of methodological problems, such as insufficient use of washout periods in crossover designs, heterogeneous classification of seizures and infrequent use of statistics in the evaluation of side effects. On the basis of controlled trials demonstrating the antiepileptic effect of VPA and GVG, methodological considerations in defining so-called therapeutic serum levels are discussed. The majority of studies that have formed the basis for establishing such levels seem methodologically insufficient, since the individual patient has only infrequently been evaluated at different drug concentrations. A study of VPA, comprising a double-blind design with multiple crossover, investigated patients at pre-established serum levels in a randomized sequence. This approach favours the view that comparison of the clinical effect of different serum levels of one drug corresponds methodologically to a comparison of the clinical effect of different drugs. Perspectives for the future development of new antiepileptic drugs and for the clinical testing of these compounds are presented." @default.
• W2137202579 created "2016-06-24" @default.
• W2137202579 creator A5042475896 @default.
• W2137202579 date "1988-10-01" @default.
• W2137202579 modified "2023-09-27" @default.
• W2137202579 title "Experimental studies and controlled clinical testing of valproate and vigabatrin" @default.
• W2137202579 cites W1152299788 @default.
• W2137202579 cites W1494332458 @default.
• W2137202579 cites W1596043277 @default.
• W2137202579 cites W1965438133 @default.
• W2137202579 cites W1966457006 @default.
• W2137202579 cites W1966574228 @default.
• W2137202579 cites W1967173426 @default.
• W2137202579 cites W1967586817 @default.
• W2137202579 cites W1967754838 @default.
• W2137202579 cites W1967794225 @default.
• W2137202579 cites W1968145606 @default.
• W2137202579 cites W1971489137 @default.
• W2137202579 cites W1972649872 @default.
• W2137202579 cites W1972973827 @default.
• W2137202579 cites W1973381993 @default.
• W2137202579 cites W1973680181 @default.
• W2137202579 cites W1973691008 @default.
• W2137202579 cites W1975590432 @default.
• W2137202579 cites W1975829798 @default.
• W2137202579 cites W1976305812 @default.
• W2137202579 cites W1977065068 @default.
• W2137202579 cites W1977221546 @default.
• W2137202579 cites W1977778648 @default.
• W2137202579 cites W1978139201 @default.
• W2137202579 cites W1979070273 @default.
• W2137202579 cites W1980117682 @default.
• W2137202579 cites W1980415237 @default.
• W2137202579 cites W1982258592 @default.
• W2137202579 cites W1982460317 @default.
• W2137202579 cites W1984114233 @default.
• W2137202579 cites W1984899272 @default.
• W2137202579 cites W1985313023 @default.
• W2137202579 cites W1987625666 @default.
• W2137202579 cites W1987968485 @default.
• W2137202579 cites W1988376665 @default.
• W2137202579 cites W1989604505 @default.
• W2137202579 cites W1989836507 @default.
• W2137202579 cites W1991097268 @default.
• W2137202579 cites W1991459355 @default.
• W2137202579 cites W1993756785 @default.
• W2137202579 cites W1994457839 @default.
• W2137202579 cites W1995018101 @default.
• W2137202579 cites W1996922525 @default.
• W2137202579 cites W1997109993 @default.
• W2137202579 cites W1997636328 @default.
• W2137202579 cites W1998116658 @default.
• W2137202579 cites W1998186620 @default.
• W2137202579 cites W1998926766 @default.
• W2137202579 cites W1999268378 @default.
• W2137202579 cites W2000135760 @default.
• W2137202579 cites W2000503411 @default.
• W2137202579 cites W2002956716 @default.
• W2137202579 cites W2002976069 @default.
• W2137202579 cites W2007174839 @default.
• W2137202579 cites W2007580188 @default.
• W2137202579 cites W2008218381 @default.
• W2137202579 cites W2008820602 @default.
• W2137202579 cites W2010312199 @default.
• W2137202579 cites W2010443141 @default.
• W2137202579 cites W2011329300 @default.
• W2137202579 cites W2011853562 @default.
• W2137202579 cites W2011950043 @default.
• W2137202579 cites W2013336402 @default.
• W2137202579 cites W2013372815 @default.
• W2137202579 cites W2013441578 @default.
• W2137202579 cites W2017582281 @default.
• W2137202579 cites W2019329926 @default.
• W2137202579 cites W2020792095 @default.
• W2137202579 cites W2021278409 @default.
• W2137202579 cites W2022211892 @default.
• W2137202579 cites W2022240494 @default.
• W2137202579 cites W2022576226 @default.
• W2137202579 cites W2022828872 @default.
• W2137202579 cites W2023197185 @default.
• W2137202579 cites W2023597007 @default.
• W2137202579 cites W2025443472 @default.
• W2137202579 cites W2026614530 @default.
• W2137202579 cites W2026834024 @default.
• W2137202579 cites W2028798509 @default.
• W2137202579 cites W2030473049 @default.
• W2137202579 cites W2031774115 @default.
• W2137202579 cites W2034901987 @default.
• W2137202579 cites W2035352436 @default.
• W2137202579 cites W2036410559 @default.
• W2137202579 cites W2036443870 @default.
• W2137202579 cites W2036820209 @default.
• W2137202579 cites W2036927752 @default.
• W2137202579 cites W2037323814 @default.
• W2137202579 cites W2039733661 @default.
• W2137202579 cites W2045790097 @default.
• W2137202579 cites W2045982437 @default.
• W2137202579 cites W2046129886 @default.

• next