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F Bordier

Publications and source records attributed to F Bordier.

8 recordsLinked to original sources
PubMed2000

Effects of RPR 118723, a novel antagonist at the glycine site of the NMDA receptor, in vitro.

RPR 118723 ((8-chloro-5-methyl-2,3-dioxo-1,4-dihydro-5H-indeno[1, 2-b]pyrazin-5-yl) acetic acid) was previously reported to exhibit potent affinity for the glycine site of the N-methyl-D-aspartate (NMDA) receptor-channel complex in the nanomolar range (K(i)=3.1+/-0. 8 nM). We now report on the effects of RPR 118723 in two functional tests reflecting the interaction between the glycine site and the NMDA receptor. First, RPR 118723 potently inhibited [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) binding in the presence of NMDA (IC(50)=3.5+/-0.4 nM). Second, RPR 118723 antagonized the NMDA-induced increase in [3H]dopamine release in mouse striatal slices (IC(50)=8.0+/-1.1 nM). In both experimental models, an excess of glycine reversed the effect of RPR 118723. These results show that RPR 118723 interferes functionally in the nanomolar range with the glycine site coupled to the NMDA receptor in vitro. The blockade of the glycine site with RPR 118723 may be useful for the therapy of the disorders linked to excessive NMDA stimulation.

Animals↗
PubMed2000

The protective effect of riluzole in the MPTP model of Parkinson's disease in mice is not due to a decrease in MPP(+) accumulation.

Riluzole, has previously been shown to be protective in animal models of Parkinson's disease in vivo. In the present study the effects of riluzole on the intrastriatal formation and accumulation of MPP(+), after i.p. injection of MPTP were tested in mice, using two different experimental protocols. In the first protocol, mice were treated with a single dose (15 mg/kg i.p.) of MPTP and MPP(+) accumulation was measured 30 min, 1 h and 3 h after the injection of the toxin. Riluzole (10 mg/kg p.o.), administered 30 min before MPTP, did not modify the accumulation kinetic of MPP(+). Contrarily to riluzole, a single dose of 50 mg/kg p.o. of 7-nitroindazole (7-NI), a non-selective non hypertensive inhibitor of nitric oxide synthase (NOS), significantly decreased MPP(+) levels. In the second protocol, consisting of 3 injections of MPTP (15 mg/kg i.p.), riluzole, administered 4 times at the dose of 5 mg/kg p.o., had no effect on MPP(+) levels. The protective effect of repeated treatments of riluzole and 7-NI against MPTP-induced depletion of dopamine (DA) is also reported. Our data obtained with 7-NI (in agreement with previous studies reported by others) suggest that a part of the protection observed with this NOS inhibitor is probably due to in vivo inhibition of monoamine oxidase-B (MAO-B). That riluzole does not modify MPP(+) accumulation demonstrates that its protective effect against MPTP toxicity was not due to an in vivo interference with MPTP metabolism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

Thalidomide reduces MPTP-induced decrease in striatal dopamine levels in mice.

The effects of thalidomide, a sedative, anti-inflammatory and immunosuppressive agent were studied in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) murine model of Parkinson's disease. The striatal levels of dopamine (DA) and of its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured both in the MPTP control group (3 x 15 mg/kg intraperitoneally) and in the thalidomide groups (repeated treatments at 25 mg/kg or 50 mg/kg postoperatively). For mice treated with thalidomide, a dose-dependent protection was observed against the MPTP-induced decrease in DA. The decrease in HVA levels was totally antagonized by thalidomide at both doses. That thalidomide has activity in this model suggests that an inflammatory process may be involved in the induction of lesions by MPTP in DAergic neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Neuroprotective effects of RPR 104632, a novel antagonist at the glycine site of the NMDA receptor, in vitro.

The NMDA antagonist and neuroprotective effects of RPR 104632 (2H-1,2,4-benzothiadiazine-1-dioxide-3-carboxylic acid), a new benzothiadiazine derivative, with affinity for the glycine site of the NMDA receptor-channel complex are described. RPR 104632 antagonized the binding of [3H]5,7-dichlorokynurenic acid to the rat cerebral cortex, with a Ki of 4.9 nM. This effect was stereospecific, since the (-)-isomer was 500-fold more potent than the (+)-isomer. The potent affinity of RPR 104632 for the glycine site was confirmed by the observation that RPR 104632 inhibited [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) binding in the presence of N-methyl-D-aspartate (NMDA) (IC50 = 55 nM), whereas it had no effect on the competitive NMDA site or on the dissociative anaesthetic site. RPR 104632 inhibited the NMDA-evoked increase in guanosine 3',5'-cyclic monophosphate (cGMP) levels of neonatal rat cerebellar slices (IC50 = 890 nM) in a non-competitive manner and markedly reduced NMDA-induced neurotoxicity in rat hippocampal slices and in cortical primary cell cultures. These results suggest that RPR 104632 is a high-affinity specific antagonist of the glycine site coupled to the NMDA receptor channel with potent neuroprotective properties in vitro.

Aminoquinolines↗
PubMed1996

The antidepressant metapramine is a low-affinity antagonist at N-methyl-D-aspartic acid receptors.

Metapramine, a pharmacological compound with antidepressant activity in humans, was tested for possible antiglutamatergic activity, in vitro. We investigated the effects of metapramine on the N-methyl-D-aspartic acid (NMDA) receptor complex, by determining whether this compound would interfere with the binding of [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) to rat cortical membranes in the presence of either glycine NMDA, or both. Metapramine in the micromolar range inhibited the binding of [3H]TCP in the presence of both NMDA and glycine (IC50 = 1.4 +/- 0.2 microM). That very similar affinities were observed when either NMDA or glycine was present suggests that metapramine exerted a direct action at the PCP site. The affinity of metapramine for this site was about 25 and 350 times lower than that of PCP and MK-801, respectively. Metapramine inhibited the NMDA-evoked increase in guanosine 3',5'-cyclic monophosphate (cGMP) levels of neonatal rat cerebellar slices (IC50 = 13 microM). These results suggest that metapramine is a low-affinity antagonist of the NMDA receptor complex channel. This paper discusses the potential application of metapramine to the treatment of diseases linked to excessive stimulation of glutamatergic NMDA receptors.

Animals↗
PubMed1995

Methamphetamine and dopamine neurotoxicity: differential effects of agents interfering with glutamatergic transmission.

The effects of riluzole and lamotrigine, two agents which interfere with the release of glutamate (GLU), and MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, were compared in the model of methamphetamine-induced depletion of dopamine (DA) levels in mice. Repeated injections with methamphetamine (4 x 5 mg/kg i.p.) markedly decreased levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. When mice were treated with riluzole (2 x 10 mg/kg p.o.), no protection was observed against the decrease in DA and the two metabolites. Lamotrigine (2 x 10 mg/kg p.o.) was also inactive. Treatment with MK-801 (2 x 2.5 mg/kg i.p.) antagonized the decrease in DA, DOPAC and HVA levels induced by the neurotoxin. Thus, unlike an NMDA blocker, drugs that interfere with GLU release did not antagonize the methamphetamine-induced DA neurotoxicity in mice. The consequences of this inactivity are discussed in terms of the reliability of this model to test new drugs with putative efficacy in the treatment of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Riluzole and experimental parkinsonism: antagonism of MPTP-induced decrease in central dopamine levels in mice.

We have investigated whether riluzole, a compound that interferes with glutamatergic (GLUergic) transmission, would protect central dopaminergic (DAergic) neurones from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the striatum in mice. MPTP decreased DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Riluzole protected against the MPTP-induced decrease in DA levels. The utilization of DA ([DOPAC+HVA]/DA) was increased after MPTP treatment, but returned to control values in mice given riluzole in combination with MPTP. Riluzole did not confer protection by inhibiting either monoamine oxidase type B activity or DA uptake. Possible mechanisms involved in the protective action of riluzole are discussed. Our results show that riluzole antagonizes the DAergic neurotoxicity of MPTP, a pro-parkinsonian neurotoxin, in mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗