1,721,113 research outputs found
Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. I. Modulation of corticostriatal synaptic transmission
No full textOxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the drug's antiepileptic activity. The corticostriatal pathway is involved in the propagation of epileptic discharges. We characterized the electrophysiological effects of GP 47779 on striatal neurons by making intracellular recordings from corticostriatal slices. GP 47779 (3-100 microM) produced a dose-dependent inhibition of glutamatergic excitatory postsynaptic potentials (EPSPs). This effect was not coupled either with changes of the membrane potential of these cells or with alterations of their postsynaptic sensitivity to excitatory amino acids (EAA) suggesting a presynaptic site of action. GP 47779 reduced the current-evoked firing discharge only at concentrations > 100 microM. GP 47779 did not affect the presynaptic inhibitory action of adenosine, showing that presynaptic adenosine receptors were not implicated in the GP 47779-mediated reduction of corticostriatal EPSPs. Our data indicate that GP 47779 apparently acts directly on corticostriatal terminals to reduce the release of EAA, probably by inhibiting high-voltage-activated (HVA) calcium (Ca2+) currents (described in the accompanying article). The inhibitory action of GP 47779 on corticostriatal transmission may contribute to the antiepileptic effects of this drug
Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. I. Modulation of corticostriatal synaptic transmission
No full textOxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the drug's antiepileptic activity. The corticostriatal pathway is involved in the propagation of epileptic discharges. We characterized the electrophysiological effects of GP 47779 on striatal neurons by making intracellular recordings from corticostriatal slices. GP 47779 (3-100 microM) produced a dose-dependent inhibition of glutamatergic excitatory postsynaptic potentials (EPSPs). This effect was not coupled either with changes of the membrane potential of these cells or with alterations of their postsynaptic sensitivity to excitatory amino acids (EAA) suggesting a presynaptic site of action. GP 47779 reduced the current-evoked firing discharge only at concentrations > 100 microM. GP 47779 did not affect the presynaptic inhibitory action of adenosine, showing that presynaptic adenosine receptors were not implicated in the GP 47779-mediated reduction of corticostriatal EPSPs. Our data indicate that GP 47779 apparently acts directly on corticostriatal terminals to reduce the release of EAA, probably by inhibiting high-voltage-activated (HVA) calcium (Ca2+) currents (described in the accompanying article). The inhibitory action of GP 47779 on corticostriatal transmission may contribute to the antiepileptic effects of this drug
Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. I. Modulation of corticostriatal synaptic transmission
No full textOxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the drug's antiepileptic activity. The corticostriatal pathway is involved in the propagation of epileptic discharges. We characterized the electrophysiological effects of GP 47779 on striatal neurons by making intracellular recordings from corticostriatal slices. GP 47779 (3-100 microM) produced a dose-dependent inhibition of glutamatergic excitatory postsynaptic potentials (EPSPs). This effect was not coupled either with changes of the membrane potential of these cells or with alterations of their postsynaptic sensitivity to excitatory amino acids (EAA) suggesting a presynaptic site of action. GP 47779 reduced the current-evoked firing discharge only at concentrations > 100 microM. GP 47779 did not affect the presynaptic inhibitory action of adenosine, showing that presynaptic adenosine receptors were not implicated in the GP 47779-mediated reduction of corticostriatal EPSPs. Our data indicate that GP 47779 apparently acts directly on corticostriatal terminals to reduce the release of EAA, probably by inhibiting high-voltage-activated (HVA) calcium (Ca2+) currents (described in the accompanying article). The inhibitory action of GP 47779 on corticostriatal transmission may contribute to the antiepileptic effects of this drug
Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents
No full textGP 47779, the active metabolite of oxcarbazepine (OCBZ) inhibits glutamatergic excitatory postsynaptic potentials (EPSPs) in rat striatum (described in the accompanying article). This effect was presumed to involve the modulation of the calcium (Ca2+) signals at either pre- or postsynaptic level. Therefore, we directly tested whether GP 47779 could modulate Ca2+ conductances in cortical as well as in striatal neurons. GP 47779 produced a reversible dose-dependent decrease in high-voltage-activated (HVA) Ca2+ currents evoked by membrane depolarization in isolated cortical pyramidal cells. GP 47779-mediated reduction in HVA Ca2+ currents, if occurring also at corticostriatal axon terminals, might explain the reduction of glutamate release in the striatum. An inhibitory action of GP 47779 on HVA Ca2+ currents was also observed in isolated striatal neurons. The effect of HVA Ca2+ currents in cortical and striatal neurons persisted in the presence of nifedipine, suggesting that dihydropyridine-sensitive channels were not involved in the GP 47779-mediated responses. We propose that the modulation of HVA Ca2+ channels by this carbamazepine (CBZ) analogue may account for its inhibitory action on transmitter release
Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents
No full textGP 47779, the active metabolite of oxcarbazepine (OCBZ) inhibits glutamatergic excitatory postsynaptic potentials (EPSPs) in rat striatum (described in the accompanying article). This effect was presumed to involve the modulation of the calcium (Ca2+) signals at either pre- or postsynaptic level. Therefore, we directly tested whether GP 47779 could modulate Ca2+ conductances in cortical as well as in striatal neurons. GP 47779 produced a reversible dose-dependent decrease in high-voltage-activated (HVA) Ca2+ currents evoked by membrane depolarization in isolated cortical pyramidal cells. GP 47779-mediated reduction in HVA Ca2+ currents, if occurring also at corticostriatal axon terminals, might explain the reduction of glutamate release in the striatum. An inhibitory action of GP 47779 on HVA Ca2+ currents was also observed in isolated striatal neurons. The effect of HVA Ca2+ currents in cortical and striatal neurons persisted in the presence of nifedipine, suggesting that dihydropyridine-sensitive channels were not involved in the GP 47779-mediated responses. We propose that the modulation of HVA Ca2+ channels by this carbamazepine (CBZ) analogue may account for its inhibitory action on transmitter release
Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents
No full textGP 47779, the active metabolite of oxcarbazepine (OCBZ) inhibits glutamatergic excitatory postsynaptic potentials (EPSPs) in rat striatum (described in the accompanying article). This effect was presumed to involve the modulation of the calcium (Ca2+) signals at either pre- or postsynaptic level. Therefore, we directly tested whether GP 47779 could modulate Ca2+ conductances in cortical as well as in striatal neurons. GP 47779 produced a reversible dose-dependent decrease in high-voltage-activated (HVA) Ca2+ currents evoked by membrane depolarization in isolated cortical pyramidal cells. GP 47779-mediated reduction in HVA Ca2+ currents, if occurring also at corticostriatal axon terminals, might explain the reduction of glutamate release in the striatum. An inhibitory action of GP 47779 on HVA Ca2+ currents was also observed in isolated striatal neurons. The effect of HVA Ca2+ currents in cortical and striatal neurons persisted in the presence of nifedipine, suggesting that dihydropyridine-sensitive channels were not involved in the GP 47779-mediated responses. We propose that the modulation of HVA Ca2+ channels by this carbamazepine (CBZ) analogue may account for its inhibitory action on transmitter release
A field potential analysis on the effects of lamotrigine, GP 47779, and felbamate in neocortical slices
No full textwe studied the action of the new antiepileptic drugs lamotrigine (LTG), GP 47779 (the active metabolite of oxcarbazepine), and felbamate (FBM) on stimulus-evoked field potentials recorded from rat prefrontal and frontal cortical slices. In the presence of physiologic concentrations of extracellular magnesium (1.2 mM) the field potential amplitude was not affected by the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, 2-amino-5-phosphonovalerate (APV), while it was blocked by the non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). when magnesium was removed from the bathing medium, there was a significant NMDA-mediated component of the field potential. LTG and GP 47779 decreased, in a dose-dependent manner, the field potential amplitude under both experimental conditions. FBM caused a dose-related decrease of the field potential amplitude only in the absence of external magnesium, suggesting a selective interaction with an NMDA-mediated component of this potential. these findings indicate that the reduction of cortical excitatory transmission might represent a common target for new antiepileptic drugs
A field potential analysis on the effects of lamotrigine, GP 47779, and felbamate in neocortical slices
No full textWe studied the action of the new antiepileptic drugs lamotrigine (LTG), GP 47779 (the active metabolite of oxcarbazepine), and felbamate (FBM) on stimulus-evoked field potentials recorded from rat prefrontal and frontal cortical slices. In the presence of physiologic concentrations of extracellular magnesium (1.2 mM) the field potential amplitude was not affected by the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, 2-amino-5-phosphonovalerate (APV), while it was blocked by the non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When magnesium was removed from the bathing medium, there was a significant NMDA-mediated component of the field potential. LTG and GP 47779 decreased, in a dose-dependent manner, the field potential amplitude under both experimental conditions. FBM caused a dose-related decrease of the field potential amplitude only in the absence of external magnesium, suggesting a selective interaction with an NMDA-mediated component of this potential. These findings indicate that the reduction of cortical excitatory transmission might represent a common target for new antiepileptic drugs
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
