Soubrie P

References (10)

Title : Neurochemical, electrophysiological and pharmacological profiles of the selective inhibitor of the glycine transporter-1 SSR504734, a potential new type of antipsychotic - Depoortere_2005_Neuropsychopharmacology_30_1963
Author(s) : Depoortere R , Dargazanli G , Estenne-Bouhtou G , Coste A , Lanneau C , Desvignes C , Poncelet M , Heaulme M , Santucci V , Decobert M , Cudennec A , Voltz C , Boulay D , Terranova JP , Stemmelin J , Roger P , Marabout B , Sevrin M , Vige X , Biton B , Steinberg R , Francon D , Alonso R , Avenet P , Oury-Donat F , Perrault G , Griebel G , George P , Soubrie P , Scatton B
Ref : Neuropsychopharmacology , 30 :1963 , 2005
Abstract : Noncompetitive N-methyl-D-aspartate (NMDA) blockers induce schizophrenic-like symptoms in humans, presumably by impairing glutamatergic transmission. Therefore, a compound potentiating this neurotransmission, by increasing extracellular levels of glycine (a requisite co-agonist of glutamate), could possess antipsychotic activity. Blocking the glycine transporter-1 (GlyT1) should, by increasing extracellular glycine levels, potentiate glutamatergic neurotransmission. SSR504734, a selective and reversible inhibitor of human, rat, and mouse GlyT1 (IC50=18, 15, and 38 nM, respectively), blocked reversibly the ex vivo uptake of glycine (mouse cortical homogenates: ID50: 5 mg/kg i.p.), rapidly and for a long duration. In vivo, it increased (minimal efficacious dose (MED): 3 mg/kg i.p.) extracellular levels of glycine in the rat prefrontal cortex (PFC). This resulted in an enhanced glutamatergic neurotransmission, as SSR504734 potentiated NMDA-mediated excitatory postsynaptic currents (EPSCs) in rat hippocampal slices (minimal efficacious concentration (MEC): 0.5 microM) and intrastriatal glycine-induced rotations in mice (MED: 1 mg/kg i.p.). It normalized activity in rat models of hippocampal and PFC hypofunctioning (through activation of presynaptic CB1 receptors): it reversed the decrease in electrically evoked [3H]acetylcholine release in hippocampal slices (MEC: 10 nM) and the reduction of PFC neurons firing (MED: 0.3 mg/kg i.v.). SSR504734 prevented ketamine-induced metabolic activation in mice limbic areas and reversed MK-801-induced hyperactivity and increase in EEG spectral energy in mice and rats, respectively (MED: 10-30 mg/kg i.p.). In schizophrenia models, it normalized a spontaneous prepulse inhibition deficit in DBA/2 mice (MED: 15 mg/kg i.p.), and reversed hypersensitivity to locomotor effects of d-amphetamine and selective attention deficits (MED: 1-3 mg/kg i.p.) in adult rats treated neonatally with phencyclidine. Finally, it increased extracellular dopamine in rat PFC (MED: 10 mg/kg i.p.). The compound showed additional activity in depression/anxiety models, such as the chronic mild stress in mice (10 mg/kg i.p.), ultrasonic distress calls in rat pups separated from their mother (MED: 1 mg/kg s.c.), and the increased latency of paradoxical sleep in rats (MED: 30 mg/kg i.p.). In conclusion, SSR504734 is a potent and selective GlyT1 inhibitor, exhibiting activity in schizophrenia, anxiety and depression models. By targeting one of the primary causes of schizophrenia (hypoglutamatergy), it is expected to be efficacious not only against positive but also negative symptoms, cognitive deficits, and comorbid depression/anxiety states.
ESTHER : Depoortere_2005_Neuropsychopharmacology_30_1963
PubMedSearch : Depoortere_2005_Neuropsychopharmacology_30_1963
PubMedID: 15956994

Title : The new neurokinin 1-sensitive receptor mediates the facilitation by endogenous tachykinins of the NMDA-evoked release of acetylcholine after suppression of dopaminergic transmission in the matrix of the rat striatum - Kemel_2003_J.Neurochem_87_487
Author(s) : Kemel ML , Perez S , Beaujouan JC , Jabourian M , Soubrie P , Glowinski J
Ref : Journal of Neurochemistry , 87 :487 , 2003
Abstract : Using an in vitro microsuperfusion procedure, the NMDA-evoked release of [3H]ACh was studied after suppression of dopamine (DA) transmission (alpha-methyl-p-tyrosine) in striatal compartments of the rat. The effects of tachykinin neurokinin 1 (NK1) receptor antagonists and the ability of appropriate agonists to counteract the antagonist responses were investigated to determine whether tachykinin NK1 classic, septide-sensitive and/or new NK1-sensitive receptors mediate these regulations. The NK1 antagonists, SR140333, SSR240600, GR205171 but not GR82334 and RP67580 (0.1 and 1 microM) markedly reduced the NMDA (1 mm + D-serine 10 microM)-evoked release of [3H]ACh only in the matrix. These responses unchanged by coapplication with NMDA of NK2 or NK3 agonists, [Lys5,MeLeu9,Nle10]NKA(4-10) or senktide, respectively, were completely counteracted by the selective NK1 agonist, [Pro9]substance P but also by neurokinin A and neuropeptide K (1 nM each). According to the rank order of potency of agonists for counteracting the antagonist responses ([Pro9]substance P, 0.013 nM > neurokinin A, 0.15 nM >> substance P(6-11) 7.7 nM = septide 8.7 nM), the new NK1-sensitive receptors mediate the facilitation by endogenous tachykinins of the NMDA-evoked release of ACh in the matrix, after suppression of DA transmission. Solely the NK1 antagonists having a high affinity for these receptors could be used as indirect anti-cholinergic agents.
ESTHER : Kemel_2003_J.Neurochem_87_487
PubMedSearch : Kemel_2003_J.Neurochem_87_487
PubMedID: 14511126

Title : SSR591813, a novel selective and partial alpha4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation - Cohen_2003_J.Pharmacol.Exp.Ther_306_407
Author(s) : Cohen C , Bergis OE , Galli F , Lochead AW , Jegham S , Biton B , Leonardon J , Avenet P , Sgard F , Besnard F , Graham D , Coste A , Oblin A , Curet O , Voltz C , Gardes A , Caille D , Perrault G , George P , Soubrie P , Scatton B
Ref : Journal of Pharmacology & Experimental Therapeutics , 306 :407 , 2003
Abstract : (5aS,8S,10aR)-5a,6,9,10-Tetrahydro,7H,11H-8,10a-methanopyrido[2',3':5,6]pyrano[2, 3-d]azepine (SSR591813) is a novel compound that binds with high affinity to the rat and human alpha4beta2 nicotinic acetylcholine receptor (nAChR) subtypes (Ki = 107 and 36 nM, respectively) and displays selectivity for the alpha4beta2 nAChR (Ki, human alpha3beta4 > 1000, alpha3beta2 = 116; alpha1beta1deltagamma > 6000 nM and rat alpha7 > 6000 nM). Electrophysiological experiments indicate that SSR591813 is a partial agonist at the human alpha4beta2 nAChR subtype (EC50 = 1.3 micro M, IA =19% compared with the full agonist 1,1-dimethyl-4-phenyl-piperazinium). In vivo findings from microdialysis and drug discrimination studies confirm the partial intrinsic activity of SSR591813. The drug increases dopamine release in the nucleus accumbens shell (30 mg/kg i.p.) and generalizes to nicotine or amphetamine (10-20 mg/kg i.p.) in rats, with an efficacy approximately 2-fold lower than that of nicotine. Pretreatment with SSR591813 (10 mg/kg i.p.) reduces the dopamine-releasing and discriminative effects of nicotine. SSR591813 shows activity in animal models of nicotine dependence at doses devoid of unwanted side effects typically observed with nicotine (hypothermia and cardiovascular effects). The compound (10 mg/kg i.p.) also prevents withdrawal signs precipitated by mecamylamine in nicotine-dependent rats and partially blocks the discriminative cue of an acute precipitated withdrawal. SSR591813 (20 mg/kg i.p.) reduces i.v. nicotine self-administration and antagonizes nicotine-induced behavioral sensitization in rats. The present results confirm important role for alpha4beta2 nAChRs in mediating nicotine dependence and suggest that SSR591813, a partial agonist at this particular nAChR subtype, may have therapeutic potential in the clinical management of smoking cessation.
ESTHER : Cohen_2003_J.Pharmacol.Exp.Ther_306_407
PubMedSearch : Cohen_2003_J.Pharmacol.Exp.Ther_306_407
PubMedID: 12682217

Title : Facilitation by endogenous tachykinins of the NMDA-evoked release of acetylcholine after acute and chronic suppression of dopaminergic transmission in the matrix of the rat striatum - Kemel_2002_J.Neurosci_22_1929
Author(s) : Kemel ML , Perez S , Godeheu G , Soubrie P , Glowinski J
Ref : Journal of Neuroscience , 22 :1929 , 2002
Abstract : Using a microsuperfusion method in vitro, the effects of the NK1, NK2, and NK3 tachykinin receptor antagonists SR140333, SR48968, and SR142801, respectively, on the NMDA-evoked release of [3H]-acetylcholine were investigated after both acute and chronic suppression of dopamine transmission in striosomes and matrix of the rat striatum. NMDA (1 mm) alone or with D-serine (10 microm) in the presence of alpha-methyl-p-tyrosine (100 microm) markedly enhanced the release of [3H]-acetylcholine through a dopamine-independent inhibitory process. In both conditions, as well as after chronic 6-OHDA-induced denervation of striatal dopaminergic fibers, SR140333, SR48968, or SR142801 (0.1 microm each) reduced the NMDA-evoked release of [3H]-acetylcholine in the matrix but not in striosome-enriched areas. These responses were selectively abolished by coapplication with NMDA of the respective tachykinin agonists, septide, [Lys5,MeLeu9,Nle10]NKA(4-10), or senktide. Distinct mechanisms are involved in the effects of the tachykinin antagonists because the inhibitory response of SR140333 was additive with that of either SR48968 or SR142801. In addition, the SR140333-evoked response remained unchanged, whereas those of SR48968 and SR142801 were abolished in the presence of N(G)-monomethyl-l-arginine (nitric oxide synthase inhibitor). Therefore, in the matrix but not in striosomes, the acute or chronic suppression of dopamine transmission unmasked the facilitatory effects of endogenously released substance P, neurokinin A, and neurokinin B on the NMDA-evoked release of [3H]-acetylcholine. Whereas substance P and neurokinin A are colocalized in same efferent neurons, their responses involve distinct circuits because the substance P response seems to be mediated by NK1 receptors located on cholinergic interneurons, while those of neurokinin A and neurokinin B are nitric oxide-dependent.
ESTHER : Kemel_2002_J.Neurosci_22_1929
PubMedSearch : Kemel_2002_J.Neurosci_22_1929
PubMedID: 11880523

Title : SL65.0155, A Novel 5-Hydroxytryptamine(4) Receptor Partial Agonist with Potent Cognition-Enhancing Properties - Moser_2002_J.Pharmacol.Exp.Ther_302_731
Author(s) : Moser PC , Bergis OE , Jegham S , Lochead A , Duconseille E , Terranova JP , Caille D , Berque-Bestel I , Lezoualc'h F , Fischmeister R , Dumuis A , Bockaert J , George P , Soubrie P , Scatton B
Ref : Journal of Pharmacology & Experimental Therapeutics , 302 :731 , 2002
Abstract : SL65.0155 [5-(8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-[1-(2-phenyl ethyl)-4-piperidinyl]-1,3,4-oxadiazol-2(3H)-one monohydrochloride] is a novel benzodioxanoxadiazolone compound with high affinity for human 5-hydroxytryptamine (5-HT)(4) receptors (K(i) of 0.6 nM) and good selectivity (greater than 100-fold for all other receptors tested). In cells expressing the 5-HT(4(b)) and 5-HT(4(e)) splice variants, SL65.0155 acted as a partial agonist, stimulating cAMP production with a maximal effect of 40 to 50% of serotonin. However, in the rat esophagus preparation, SL65.0155 acted as a 5-HT(4) antagonist with a pK(b) of 8.81. In addition, SL65.0155 potently improved performance in several tests of learning and memory. In the object recognition task, it improved retention at 24 h when administered i.p. or p.o. (0.001-0.1 mg/kg). This effect was antagonized by the 5-HT(4) antagonist SDZ 205,557, itself without effect, demonstrating that the promnesic effects of SL65.0155 are mediated by 5-HT(4) agonism. SL65.0155 also reversed the cognitive deficits of aged rats in the linear maze task and the scopolamine-induced deficit of mice in the water maze task. Furthermore, the combined administration of an inactive dose of SL65.0155 with the cholinesterase inhibitor rivastigmine resulted in a significant promnesic effect, suggesting a synergistic interaction. SL65.0155 was devoid of unwanted cardiovascular, gastrointestinal, or central nervous system effects with doses up to more than 100-fold higher than those active in the cognitive tests. These results characterize SL65.0155 as a novel promnesic agent acting via 5-HT(4) receptors, with an excellent preclinical profile. Its broad range of activity in cognitive tests and synergism with cholinesterase inhibitors suggest that SL65.0155 represents a promising new agent for the treatment of dementia.
ESTHER : Moser_2002_J.Pharmacol.Exp.Ther_302_731
PubMedSearch : Moser_2002_J.Pharmacol.Exp.Ther_302_731
PubMedID: 12130738

Title : 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylp henyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A): a potent and selective corticotrophin-releasing factor(1) receptor antagonist. I. Biochemical and pharmacological characterization - Gully_2002_J.Pharmacol.Exp.Ther_301_322
Author(s) : Gully D , Geslin M , Serva L , Fontaine E , Roger P , Lair C , Darre V , Marcy C , Rouby PE , Simiand J , Guitard J , Gout G , Steinberg R , Rodier D , Griebel G , Soubrie P , Pascal M , Pruss R , Scatton B , Maffrand JP , Le Fur G
Ref : Journal of Pharmacology & Experimental Therapeutics , 301 :322 , 2002
Abstract : 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1- (3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A), a new 2-aminothiazole derivative, shows nanomolar affinity for human cloned or native corticotrophin-releasing factor (CRF)(1) receptors (pK(i) values of 8.73 and 9.08, respectively), and a 1000-fold selectivity for CRF(1) versus CRF(2 alpha) receptor and CRF binding protein. SSR125543A antagonizes CRF-induced stimulation of cAMP synthesis in human retinoblastoma Y 79 cells (IC(50) = 3.0 +/- 0.4 nM) and adrenocorticotropin hormone (ACTH) secretion in mouse pituitary tumor AtT-20 cells. SSR125543A is devoid of agonist activity in these models. Its brain penetration was demonstrated in rats by using an ex vivo [(125)I-Tyr(0)] ovine CRF binding assay. SSR125543A displaced radioligand binding to the CRF(1) receptor in the brain with an ID(50) of 6.5 mg/kg p.o. (duration of action >24 h). SSR125543A also inhibited the increase in plasma ACTH levels elicited in rats by i.v. CRF (4 microg/kg) injection (ID(50) = 1, 5, or 5 mg/kg i.v., i.p., and p.o., respectively); this effect lasted for more than 6 h when the drug was given orally at a dose of 30 mg/kg. SSR125543A (10 mg/kg p.o.) reduced by 73% the increase in plasma ACTH levels elicited by a 15-min restraint stress in rats. Moreover, SSR125543A (20 mg/kg i.p.) also antagonized the increase of hippocampal acetylcholine release induced by i.c.v. injection of 1 microg of CRF in rats. Finally, SSR125543A reduced forepaw treading induced by i.c.v. injection of 1 microg of CRF in gerbils (ID(50) = approximately 10 mg/kg p.o.). Altogether, these data indicate that SSR125543A is a potent, selective, and orally active CRF(1) receptor antagonist.
ESTHER : Gully_2002_J.Pharmacol.Exp.Ther_301_322
PubMedSearch : Gully_2002_J.Pharmacol.Exp.Ther_301_322
PubMedID: 11907190

Title : Administration of amyloid beta-peptides in the rat medial septum causes memory deficits: reversal by SR 57746A, a non-peptide neurotrophic compound - Terranova_1996_Neurosci.Lett_213_79
Author(s) : Terranova JP , Kan JP , Storme JJ , Perreaut P , Le Fur G , Soubrie P
Ref : Neuroscience Letters , 213 :79 , 1996
Abstract : Different putative toxic amyloid beta (A beta) peptides, beta (1-42), beta (1-40) and beta (25-35), were infused (0.75, 1.5 or 3 nmol) in the rat medial septum. Memory deficits were then investigated using the social recognition test. A significant amnesia was observed 4, 7 and 14 days after intraseptal injection of 3 nmol of beta (1-42), beta-(1-40)- and beta (25-35). Lower amounts of beta (1-42) were inactive except 1.5 nmol that disrupted memory 7 days post-treatment. Used as control, the inverted peptide beta (40-1) and the scrambled beta (25-35) were inactive. Using the prolongation procedure, rats infused with 3 nmol of beta (1-40) were still able to recognize the same juvenile. Finally, a daily treatment with the non-peptide neurotrophic compound SR 57746A (10 mg/kg p.o.) over 21 days, prevented the deficits in short-term memory induced by the intraseptal infusion of 3 nmol of either beta (1-40) or beta (25-35). These findings suggest that A beta fragments could impair short-term memory when infused in the rat medial septum, an effect that is prevented by SR 57746A.
ESTHER : Terranova_1996_Neurosci.Lett_213_79
PubMedSearch : Terranova_1996_Neurosci.Lett_213_79
PubMedID: 8858613

Title : Protective effects of SR 57746A in central and peripheral models of neurodegenerative disorders in rodents and primates - Fournier_1993_Neurosci_55_629
Author(s) : Fournier J , Steinberg R , Gauthier T , Keane PE , Guzzi U , Coude FX , Bougault I , Maffrand JP , Soubrie P , Le Fur G
Ref : Neuroscience , 55 :629 , 1993
Abstract : Compounds possessing neurotrophic properties may represent a possible treatment for neurodegenerative disorders such as Alzheimer's disease. SR 57746A, 1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride, is a new compound with neurotrophic activity in a number of in vitro preparations. The neurotrophic effects of this compound have been evaluated in vivo using four distinct rat models of neurodegeneration: transient global ischaemia produced by a four-vessel occlusion; septohippocampal lesion produced by injection of vincristine sulphate into the medial septum; sciatic nerve crushing; and acrylamide-induced peripheral neuropathy. Rats were administered vehicle or 2.5-10 mg/kg p.o. SR 57746A, after initiation of the degenerative process, then once daily for 10 days in the first two models, 16 days in the third and 26 days in the fourth model. Median scores for ischaemia-induced neuronal damage were reduced by 30-40% by SR 57746A treatment in hippocampal CA1, CA2, and CA3 regions, and in the dorsal striatum. Twelve days after intraseptal vincristine administration, there was a marked loss of septohippocampal cholinergic neurons, as indicated by reduced choline acetyltransferase activity in both the septum and hippocampus. SR 57746A dose-dependently reversed this reduction in both areas. These results were confirmed by histoenzymological evaluation of hippocampal acetylcholinesterase content. SR 57746A also reversed the loss of hippocampal choline acetyltransferase induced by intraseptal vincristine in marmosets. Behavioral deficits in these models (exploratory behaviour in the former and short-term social memory in the latter) were also significantly reduced by SR 57746A treatment. In the sciatic crush model, sensorimotor function improved more rapidly in rats treated with 10 mg/kg SR 57746A. In this same model, SR 57746A (10 mg/kg/day) also significantly increased the length of regenerated nerve eight days after the crush, as measured using the pinch test. Finally, SR 57746A retarded the onset, reduced the amplitude and accelerated the recovery of acrylamide-induced peripheral neuropathy. Thus, SR 57746A possesses notable neurotrophic activity in a variety of neurodegenerative models in vivo, suggesting that the compound may possess therapeutic potential for the treatment of neurodegenerative diseases.
ESTHER : Fournier_1993_Neurosci_55_629
PubMedSearch : Fournier_1993_Neurosci_55_629
PubMedID: 8413926

Title : Effects of repeated administration of tetrahydroaminoacridine (THA) on muscarinic receptor subtypes in the rat brain - Alonso_1990_Neurochem.Int_17_457
Author(s) : Alonso R , Kan JP , Worms P , Soubrie P
Ref : Neurochem Int , 17 :457 , 1990
Abstract : The effects of a chronic treatment (21 days) with the acetylcholinesterase (AChE) inhibitor tetrahydroaminoacridine (THA) on muscarinic receptors subtypes were investigated at various times after the last administration of the drug, in various brain areas including cortex, striatum, hippocampus and cerebellum. Forty eight hours after the end of chronic THA treatment, the number of muscarinic receptors, labelled with [(3)H]NMS, was significantly lowered in the cortex and the striatum but not in the hippocampus or cerebellum. High affinity pirenzepine binding sites (M(1) receptors), directly assayed using [(3)H]pirenzepine saturation assays or estimated by pirenzepine [(3)H]NMS competition, were lowered only in the cortex and in the striatum of THA-treated rats. In contrast, the number of low affinity pirenzepine sites (M(2) receptors), was not significantly modified. At shorter wash-out period (18 h), the density of M(1) receptors decreased by 26, 46 and 52% in the hippocampus, cerebral cortex and striatum, respectively. In all cases, K(d) values remained unchanged suggesting that the loss of M(1) sites was not due to a modification of radioligand affinity for the receptors. Although THA displayed a micromolar affinity for M(1) and M(2) receptors in vitro, this AChE inhibitor did not interfere with the receptor assays since no trace of residual free THA was detected in rat brain at 48 h post-treatment. These results suggest that chronic treatment with THA produced a selective down-regulation of M(1) receptors; they also indicate that these receptors may be regulated differently in cortical, striatal, hippocampal or cerebellar regions.
ESTHER : Alonso_1990_Neurochem.Int_17_457
PubMedSearch : Alonso_1990_Neurochem.Int_17_457
PubMedID: 20504646

Title : Poster: Effects of THA on acetylcholinesterase and muscannic receptors after single and repeated injection in rat -
Author(s) : Alonso R , Kan JP , Worms P , Soubrie P
Ref : Trends in Pharmacological Sciences , Suppl :105 , 1989
PubMedID: