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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 33-39 
    ISSN: 1432-1912
    Schlagwort(e): Key words Retigabine ; Anticonvulsant ; Antiepileptic ; New drug ; Field potential ; Bicuculline
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The purpose of this study was to evaluate the effects of the new anticonvulsant drug N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid ethyl ester (retigabine, D-23129, ASTA Medica, Dresden, Germany) on different patterns of epileptiform activity induced by 4-aminopyridine (4AP) in rat entorhinal cortex hippocampal slices. Application of 4AP (100 µM) induced in entorhinal cortex two different types of epileptiform activities; seizure-like events (SLE) and interictal epileptiform discharges (IED). Bicuculline (10 µM) changed 4AP-induced SLE and IED to recurrent epileptiform discharges (RED). IED were isolated after blockade of the SLE by glutamate receptor antagonists for α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors, i.e. 1,2,3,4 tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX, 10 µM) and 2-amino-5-phosphonovaleric acid (APV, 30 µM). Anticonvulsant properties of retigabine were evaluated as effect on the frequency and amplitude of SLE, IED and RED. Retigabine suppressed all types of epileptiform events in a dose dependent and reversible manner. SLE were suppressed in 71.4 and 100% of slices by 5 and 10 µM, respectively. The frequency of IED was significantly reduced by 20 µM retigabine (40.9±24.5%) and IED were blocked completely by 50 µM retigabine. When IED were isolated by application of glutamate antagonists 20 µM retigabine was sufficient to block this activity completely. RED induced by combined application of bicuculline and 4AP were blocked in 71.4% of the tested slices with 100 µM retigabine. The frequency of the RED in the remaining slices was reduced by 96.1±6.1%. We conclude that retigabine acts on a large variety of different epileptiform activities in temporal lobe structures that are known to develop readily pharmacoresistant seizures.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-1106
    Schlagwort(e): Calcium ; Hippocampal slice ; CA1 ; ω-Agatoxin IVA ; ω-Conotoxin GVIA ; ω-Conotoxin ; MVIIC ; Nimodipine ; Ethosuximide ; Trimethadion ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The contribution of T-, L-, N-, P-, and Q-type Ca2+ channels to pre-and postsynaptic Ca2+ entry during stimulus-induced high neuronal activity in area CA1 of rat hippocampal slices was investigated by measuring the effect of specific blockers on stimulus-induced decreases in extracellular Ca2+ concentration ([Ca2+]0). [Ca2+]0 was measured with ion-selective electrodes in stratum radiatum (SR) and stratum pyramidale (SP), while Ca2+ entry into neurons was induced with stimulus trains (20 Hz for 10 s) alternately delivered to SR and the alveus, respectively. The [Ca2+]0 decreases recorded in SR in response to SR stimulation represented mainly presynaptic Ca2+ entry (Capre), while [Ca2+]0 decreases recorded in SP in response to alvear stimulation were predominantly based on postsynaptic Ca2+ entry (Capost). Ethosuximide and trimethadione were ineffective m concentrations up to 1 mM. At 10 mM, they reduced Capost and, much less, also Capre Nimodipine (25 μM) reduced Capost and, to a minor extent, Capre. ω-Agatoxin IVA (0.4–1 μM) and ω-conotoxin MVIIC (1 μM) also reduced both Capre and Capost, but with a stronger action on Capre. ω-Conotoxin GVIA (3–8 μM) reduced Capost without effect on Capre. We conclude that during stimulus-induced, high-frequency neuronal activity Capost is carried by P/Q-, N-, and L-type channels and probably a further channel type different from these channels. Capre includes at least P/Q-and possibly L-type channels. N-type channels did not contribute to Capre in our experiments. Since ethosuximide and trimethadione were only effective in high concentrations, their action may be unspecific. Thus, T-type channels do not seem to play a major part in Ca2+ entry in this situation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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