The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents
; Hans, Grégory ; Nguyen, Laurent et al
in British Journal of Pharmacology (2002), 136(5), 659-672
1 In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra(R)) may involve modulation of inhibitory ... [more ▼]
1 In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra(R)) may involve modulation of inhibitory neurotransmission. 2 GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compared with reference anti-epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide. 3 LEV contrasted the reference AEDs by an absence of any direct effect on glycine-gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA-gated currents. A similar action on GABA-elicited currents was observed with the reference AEDs, except ethosuximide. 4 These minor direct effects contrasted with a potent ability of LEV (EC50 = 1-10 muM) to reverse the inhibitory effects of the negative allosteric modulators zinc and beta-carbolines on both GABA(A) and glycine receptor-mediated responses. 5 Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of beta-carbolines on GABA-gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine-gated currents and only clonazepam and phenobarbital inhibited the action of DMCM. 6 LEV (17 mg kg(-1)) produced a potent suppression of sound-induced clonic convulsions in mice. This protective effect was significantly abolished by co-administration of the beta-carboline FG 7142, from a dose of 5 mg kg(-1). In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg(-1)) was without any effect on the protection afforded by LEV. 7 The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti-epileptic mechanism(s) of action of LEV. [less ▲]Detailed reference viewed: 76 (25 ULg)
Development of a new in vivo tracer of the cerebral pH.
Plenevaux, Alain ; ; et al
in Journal of Cerebral Blood Flow & Metabolism (1989), 9S1Detailed reference viewed: 5 (2 ULg)
Evaluation of [73Se]PROMOSE as a tracer of the human cerebral pH.
; ; Plenevaux, Alain et al
Poster (1988, October 10)Detailed reference viewed: 6 (2 ULg)
Plasminogen activators in developing peripheral nervous system, cellular origin and mitogenic effect.
; Leprince, Pierre ; Rogister, Bernard et al
in Brain Research (1987), 433(1), 101-8
Newborn rat dorsal root ganglia release two different plasminogen activators (PAs): the urokinase (UK) and the tissue (tPA) type. The former is secreted by neurons while the latter is secreted by Schwann ... [more ▼]
Newborn rat dorsal root ganglia release two different plasminogen activators (PAs): the urokinase (UK) and the tissue (tPA) type. The former is secreted by neurons while the latter is secreted by Schwann cells. tPA release by Schwann cells is modulated by choleratoxin, a known mitogen for these cells. UK but not tPA stimulates in a dose-dependent fashion the proliferation of Schwann cells. This effect is observed in the absence of plasminogen, suggesting that the substrate for PAs in the developing nervous system is not plasminogen. Since UK is secreted by neurons, our data suggest a new mechanism for neuronal control of Schwann cell proliferation. [less ▲]Detailed reference viewed: 46 (33 ULg)
Potassium-induced release of neurotoxic activity by astrocytes
Lefebvre, Philippe ; Rogister, Bernard ; et al
in Brain Research (1987), 413Detailed reference viewed: 13 (11 ULg)
Laminin promotes cerebellar granule cells migration in vitro and is synthesized by cultured astrocytes
SELAK, Ivan ; Foidart, Jean-Michel ; Moonen, Gustave
in Developmental Neuroscience (1985), 7(5-6), 278-285Detailed reference viewed: 4 (0 ULg)
Plasminogen activator is a mitogen for astrocytes in developing cerebellum
Moonen, Gustave ; ; Selak, Ivan et al
in Developmental Brain Research (1985), 20Detailed reference viewed: 5 (3 ULg)
Cerebellar macroneurons in serum-free cultures: evidence for instrinsic neuronotrophic and neuronotoxic activities
; SELAK, Ivan ; et al
in Brain Research (1984), 317(1), 11-19Detailed reference viewed: 2 (0 ULg)
Plasminogen activator-plasmin system and neuronal migration.
Moonen, Gustave ; ; Selak, Ivan
in Nature (1982), 298(5876), 753-5Detailed reference viewed: 4 (1 ULg)