References of "Scuvée-Moreau, Jacqueline"
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See detailEnhancing a CH-pi interaction to increase the affinity for 5-HT1A receptors
Liégeois, Jean-François ULg; Lespagnard, Marc; Meneses Salas, Elsa et al

in ACS Medicinal Chemistry Letters (2014), 5

An electrostatic interaction related to a favourable position of the distal phenyl ring and a phenylalanine residue in the binding pocket would explain the higher 5-HT1A affinity of a 4-phenyl-1,2,3,6 ... [more ▼]

An electrostatic interaction related to a favourable position of the distal phenyl ring and a phenylalanine residue in the binding pocket would explain the higher 5-HT1A affinity of a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue compared to the corresponding 4-phenylpiperazine analogue. To explore a possible reinforcement of this interaction to increase the affinity for 5-HT1A receptors, different 4-substituted-phenyl analogues were synthesized and tested. The most important increase of affinity is obtained with two electron-donating methyl groups in position 3 and 5 [less ▲]

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See detailThe 5-HT1A agonism potential of substituted-piperazine-ethyl-amide derivatives is conserved in the hexyl homologues: molecular modeling and pharmacological evaluation
Dilly, Sébastien ULg; Scuvée-Moreau, Jacqueline ULg; Wouters, Johan et al

in Journal of Chemical Information & Modeling (2011), 51(11), 2961-2966

In a series of carboxamide and sulphonamide alkyl (ethyl to hexyl) piperazine analogues, although the size of the linker is very different, ethyl and hexyl derivatives possess a high affinity for 5-HT1A ... [more ▼]

In a series of carboxamide and sulphonamide alkyl (ethyl to hexyl) piperazine analogues, although the size of the linker is very different, ethyl and hexyl derivatives possess a high affinity for 5-HT1A receptors. Docking studies clearly show that hexyl and ethyl compounds favourably interact with the binding site of the active conformation of 5-HT1A receptors, thus confirming a possible agonist profile. This activity is effectively detected in electrophysiological experiments in which all four compounds inhibit the activity of rat dorsal raphe serotonergic neurons. [less ▲]

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See detailM-type channels selectively control bursting in rat dopaminergic neurons
Drion, Guillaume ULg; Bonjean, Maxime; Waroux, Olivier ULg et al

in European Journal of Neuroscience (2010), 31

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See detailRegards croisés sur le cannabis
Seutin, Vincent ULg; Scuvée-Moreau, Jacqueline ULg; Quertemont, Etienne ULg

Book published by Mardaga (2010)

Multidisciplinary book which presents an up to date review of scientific data available on cannabis (neurobiology, toxicology, epidemiology, public health and treatment options

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See detailSK Channel blockade promotes burst firing in dorsal raphe serotonergic neurons
Rouchet, Nathalie ULg; Waroux, Olivier ULg; Lamy, Cédric ULg et al

in European Journal of Neuroscience (2008), 28(6), 1108-15

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See detailSK Channel blockade promotes bursting in vivo in dorsal raphe serotonergic neurons
Rouchet, Nathalie; Waroux, Olivier ULg; Alix, Philippe ULg et al

in Acta Physiologica (2008, May 17), 194(supll. 666), -01

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See detailStrategies pharmacologiques de modulation de l'activite du systeme nerveux central.
Phan Ba, Remy ULg; Scuvée-Moreau, Jacqueline ULg; Seutin, Vincent ULg

in Revue Médicale de Liège (2008), 63(5-6), 238-44

There are multiple pharmacological targets in the central nervous system. After reviewing the synaptic physiology and the major neurotransmitter molecules, this article describes the main strategies used ... [more ▼]

There are multiple pharmacological targets in the central nervous system. After reviewing the synaptic physiology and the major neurotransmitter molecules, this article describes the main strategies used in neuropharmacology. The concept of specificity in the central nervous system is discussed, and allows a distinction between drugs according to the degree of specificity of their action. A catalogue of pharmacological targets is presented with therapeutic examples, and an emphasis on new agents having an original mechanism of action or acting on new targets. [less ▲]

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See detailCharacterization of 4-(2-hydroxyphenyl)-1-[2 '-[N-(2 ''-pyridinyl)-p-fluorobenzamido]ethyl]piperazine (p-DMPPF) as a new potent 5-HT1A antagonist
Defraiteur, Caroline ULg; Plenevaux, Alain ULg; Scuvée-Moreau, Jacqueline ULg et al

in British Journal of Pharmacology (2007), 152(6), 952-958

Background and purpose: The identification of potent and selective radioligands for the mapping of 5-HT receptors is interesting both for clinical and experimental research. The aim of this study was to ... [more ▼]

Background and purpose: The identification of potent and selective radioligands for the mapping of 5-HT receptors is interesting both for clinical and experimental research. The aim of this study was to compare the potency of a new putative 5-HT1A receptor antagonist, p-DMPPF, (4-(2-hydroxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-fluorobenzamido]-ethyl] piperazine) with that of the well-known 5-HT1A antagonists, WAY-100635(N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide) and its fluorobenzoyl analogue, p-MPPF (4-(2-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)p-fluorobenzamido] ethyl] piperazine). Experimental approach: Single cell extracellular recordings of dorsal raphe (DR) neurones were performed in rat brain slices. The potency of each compound at antagonizing the effect of the 5-HT1A agonist, 8-OH-DPAT [8-hydroxy-2-(di-npropylamino)tetraline], was quantified using the Schild equation. The pharmacological profile of p-DMPPF was defined using competition binding assays. Key results: Consistently with a 5-HT1A receptor antagonist profile, incubation of slices with an equimolar (10 nM) concentration of each compound markedly reduced the inhibitory effect of 8-OH-DPAT on the firing rate of DR neurones, causing a significant rightward shift in its concentration-response curve. The rank order of potency of the antagonists was WAY-100635 > p-DMPPF >= p-MPPF. The sensitivity of DR neurones to the inhibitory effect of 8-OH-DPAT was found to be heterogeneous. The binding experiments demonstrated that p-DMPPF is highly selective for 5-HT1A receptors, with a K-i value of 7 nM on these receptors. Conclusions and implications: The potency of the new compound, p-DMPPF, as a 5-HT1A antagonist is similar to that of p-MPPF in our electrophysiological assay. Its selectivity towards 5-HT1A receptors makes it a good candidate for clinical development. [less ▲]

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See detailSynthesis and Radioligand Binding Studies of Bis-Isoquinolinium Derivatives as Small Conductance Ca(2+)-Activated K(+) Channel Blockers
Graulich, Amaury ULg; Dilly, Sébastien ULg; Farce, Amaury et al

in Journal of Medicinal Chemistry (2007), 50(21), 5070-5075

Starting from the scaffold of N-methyllaudanosine and N-methylnoscapine, which are known small conductance Ca2+-activated K+ channel blockers, original bis-isoquinolinium derivatives were synthezised and ... [more ▼]

Starting from the scaffold of N-methyllaudanosine and N-methylnoscapine, which are known small conductance Ca2+-activated K+ channel blockers, original bis-isoquinolinium derivatives were synthezised and evaluated using binding studies, electrophysiology, and molecular modeling. These quaternary compounds are powerful blockers, and the most active ones have 10 times more affinity for the channels than dequalinium. The unsubstituted compounds possess a weaker affinity than the analogues having a 6,7-dimethoxy- or a 6,7,8-trimethoxy substitution. The length of the linker has no influence in the alkane derivatives. In relation to the xylene derivatives, the affinities are higher for the ortho and meta isomers. These results are well corroborated by a molecular modeling study. Finally, the most effective compounds have been tested in electrophysiological experiments on midbrain dopaminergic neurons and demonstrate the blocking potential of the apamin-sensitive after-hyperpolarization. [less ▲]

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See detailNew assessment of dependency in demented patients : impact on the quality of life in informal caregivers.
Andrieu, Sandrine; Rive, Benoït; Guilhaume, Chantal et al

in Psychiatry & Clinical Neurosciences (2007), 61(3), 234-242

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See detailSynthesis and radioligand binding studies of methoxylated 1,2,3,4-tetrahydroisoquinolinium derivatives as ligands of the apamin-sensitive Ca2+- activated K+ channels
Graulich, Amaury ULg; Scuvée-Moreau, Jacqueline ULg; Alleva, Livia ULg et al

in Journal of Medicinal Chemistry (2006), 49(24), 7208-7214

Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The ... [more ▼]

Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons. [less ▲]

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See detailThe KCNQ channel opener retigabine inhibits the activity of mesencephalic dopaminergic systems of the rat
Hansen, H. H.; Ebbesen, C.; Mathiesen, C. et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2006), 318(3), 1006-1019

Homo- and heteromeric complexes of KCNQ channel subunits are the molecular correlate of the M-current, a neuron-specific voltage-dependent K+ current with a well established role in control of neural ... [more ▼]

Homo- and heteromeric complexes of KCNQ channel subunits are the molecular correlate of the M-current, a neuron-specific voltage-dependent K+ current with a well established role in control of neural excitability. We investigated the effect of KCNQ channel modulators on the activity of dopaminergic neurons in vitro and in vivo in the rat ventral mesencephalon. The firing of dopaminergic neurons recorded in mesencephalic slices was robustly inhibited in a concentration-dependent manner by the KCNQ channel opener N-(2-amino-4-(4-fluorobenzylamino)phenyl) carbamic acid ethyl ester ( retigabine). The effect of retigabine persisted in the presence of tetrodotoxin and simultaneous blockade of GABA A receptors, small-conductance calcium-activated K+ ( SK) channels, and hyperpolarization-activated (I-h) channels, and it was potently reversed by the KCNQ channel blocker 4- pyridinylmethyl-9(10H)-anthracenone (XE991), indicating a direct effect on KCNQ channels. Likewise, in vivo single unit recordings from dopaminergic neurons revealed a prominent reduction in spike activity after systemic administration of retigabine. Furthermore, retigabine inhibited dopamine synthesis and c-Fos expression in the striatum under basal conditions. Retigabine completely blocked the excitatory effect of dopamine D-2 auto-receptor antagonists. Again, the in vitro and in vivo effects of retigabine were completely reversed by preadministration of XE991. Dual immunocytochemistry revealed that KCNQ4 is the major KCNQ channel subunit expressed in all dopaminergic neurons in the mesolimbic and nigrostriatal pathways. Collectively, these observations indicate that retigabine negatively modulates dopaminergic neurotransmission, likely originating from stimulation of mesencephalic KCNQ4 channels. [less ▲]

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See detailSK channels control the firing pattern of midbrain dopaminergic neurons in vivo
Waroux, Olivier ULg; Massotte, Laurent ULg; Alleva, Livia ULg et al

in European Journal of Neuroscience (2005), 22(12), 3111-3121

A vast body of experimental in vitro work and modelling studies suggests that the firing pattern and/or rate of a majority of midbrain dopaminergic neurons may be controlled in part by Ca2+-activated K ... [more ▼]

A vast body of experimental in vitro work and modelling studies suggests that the firing pattern and/or rate of a majority of midbrain dopaminergic neurons may be controlled in part by Ca2+-activated K+ channels of the SK type. However, due to the lack of suitable tools, in vivo evidence is lacking. We have taken advantage of the development of the water-soluble, medium potency SK blocker N-methyl-laudanosine (CH3-L) to test this hypothesis in anaesthetized rats. In the lateral ventral tegmental area, CH3-L iontophoresis onto dopaminergic neurons significantly increased the coefficient of variation of their interspike intervals and the percentage of spikes generated in bursts as compared to the control condition. The effect of CH3-L persisted in the presence of a specific GABA(A) antagonist, suggesting a direct effect. It was robust and reversible, and was also observed in the substantia nigra. Control experiments demonstrated that the effect of CH3-L could be entirely ascribed to its blockade of SK channels. On the other hand, the firing pattern of noradrenergic neurons was much less affected by CH3-L. We provide here the first demonstration of a major role of SK channels in the control of the switch between tonic and burst firing of dopaminergic neurons in physiological conditions. This study also suggests a new strategy to develop modulators of the dopaminergic (DA) system, which could be of interest in the treatment of Parkinson's disease, and perhaps other diseases in which DA pathways are dysfunctional. [less ▲]

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See detailSynthesis and radioligand binding studies of C-5- and C-8-substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums as SK channel blockers related to N-methyl-laudanosine and N-methyl-noscapine
Graulich, Amaury ULg; Scuvée-Moreau, Jacqueline ULg; Seutin, Vincent ULg et al

in Journal of Medicinal Chemistry (2005), 48(15), 4972-4982

The synthesis and the 125 I-apamin binding studies of original C-5- and C-8-substituted 143,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5 ... [more ▼]

The synthesis and the 125 I-apamin binding studies of original C-5- and C-8-substituted 143,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridiniums were performed in order to find a reversible and selective SK channel blocker structurally related to N-methyl-laudanosine and N-methyl-noscapine. A bulky alkyl substituent in the C-8 position of the tetrahydroisoquinoline produces a clear increase in the affinity for the apamin sensitive binding sites. The presence of an electron-withdrawing group in the C-5 and C-8 positions is not a suitable substitution for the affinity of drugs structurally related to N-methyl-laudanosine. Thiophenic analogues and 8-methoxy derivatives possess a poor affinity for the apamin sensitive binding sites. Electrophysiological studies performed with the most effective compound showed a blockade of the apamin sensitive afterhyperpolarization in rat dopaminergic neurons. [less ▲]

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See detailSynthesis and biological evaluation of N-methyl-laudanosine iodide analogues as potential SK channel blockers.
Graulich, A.; Mercier, Frédéric ULg; Scuvée-Moreau, Jacqueline ULg et al

in Bioorganic & Medicinal Chemistry (2005), 13(4), 1201-9

Neuronal action potentials are followed by an afterhyperpolarisation (AHP), which is mediated by small conductance Ca2+-activated K+ channels (SK channels or KCa2 channels). This AHP plays an important ... [more ▼]

Neuronal action potentials are followed by an afterhyperpolarisation (AHP), which is mediated by small conductance Ca2+-activated K+ channels (SK channels or KCa2 channels). This AHP plays an important role in regulating neuronal activity and agents modulating AHP amplitude could have a potential therapeutic interest. It was previously shown that N-methyl-bicuculline iodide blocks SK channels but its GABA) activity represents a serious drawback. In view of the structural analogy between bicuculline and laudanosine 14, several N-quaternary analogues of the latter were developed. It was shown that N-methyl-laudanosine 15 (NML) and N-ethyl-laudanosine 16 induce a reversible and relatively specific blockade of the apamin sensitive AHP in dopaminergic neurones with mean IC50s of 15, and 47 microM, respectively. Laudanosine 14, N-butyl-17 and N-benzyl-18 derivatives were less potent. In order to find pharmacophore elements, modifications were performed at different positions such as C-1, C-6 and C-7. Intracellular recordings on rat midbrain dopaminergic neurones were made in order to evaluate the putative blockade of SK channels by these molecules. Simplified structures such as tetrahydroisoquinoline derivatives with H or Me at C-1 1-6 presented no significant activity at 300 microM. The presence of a 1-(3,4-dimethoxybenzyl) moiety seems an important feature. Indeed, compound 8 showed a blockade of the AHP of only 33% at 300 microM while compound 13 blocked it by 67%, respectively, at the same concentration. Binding experiments were also performed. Binding affinities for SK channels are in good agreement with electrophysiological data. These results indicate that the presence of a charged nitrogen group is an essential point for the affinity on SK channels. Finally, because of the similar activity of both enantiomers of NML 19 and 20, the interaction site may present a symmetrical configuration. [less ▲]

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See detailElectrophysiological characterization of the SK channel blockers methyl-laudanosine and methyl-noscapine in cell lines and rat brain slices
Scuvée-Moreau, Jacqueline ULg; Boland, André ULg; Graulich, Amaury ULg et al

in British Journal of Pharmacology (2004), 143(6), 753-764

We have recently shown that the alkaloid methyl-laudanosine blocks SK channel-mediated afterhyperpolarizations (AHPs) in midbrain dopaminergic neurones. However, the relative potency of the compound on ... [more ▼]

We have recently shown that the alkaloid methyl-laudanosine blocks SK channel-mediated afterhyperpolarizations (AHPs) in midbrain dopaminergic neurones. However, the relative potency of the compound on the SK channel subtypes and its ability to block AHPs of other neurones were unknown. Using whole-cell patch-clamp experiments in transfected cell lines, we found that the compound blocks SK1, SK2 and SK3 currents with equal potency: its mean IC(50)s were 1.2, 0.8 and 1.8 microM, respectively. IK currents were unaffected. In rat brain slices, methyl-laudanosine blocked apamin-sensitive AHPs in serotonergic neurones of the dorsal raphe and noradrenergic neurones of the locus coeruleus with IC(50)s of 21 and 19 microM, as compared to 15 microM in dopaminergic neurones. However, at 100 microM, methyl-laudanosine elicited a constant hyperpolarization of serotonergic neurones of about 9 mV, which was inconsistently (i.e. not in a reproducible manner) antagonized by atropine and hence partly due to the activation of muscarinic receptors. While exploring the pharmacology of related compounds, we found that methyl-noscapine also blocked SK channels. In cell lines, methyl-noscapine blocked SK1, SK2 and SK3 currents with mean IC(50)s of 5.9, 5.6 and 3.9 microM, respectively. It also did not block IK currents. Methyl-noscapine was slightly less potent than methyl-laudanosine in blocking AHPs in brain slices, its IC(50)s being 42, 37 and 29 microM in dopaminergic, serotonergic and noradrenergic neurones, respectively. Interestingly, no significant non-SK effects were observed with methyl-noscapine in slices. At a concentration of 300 microM, methyl-noscapine elicited the same changes in excitability in the three neuronal types than did a supramaximal concentration of apamin (300 nM). Methyl-laudanosine and methyl-noscapine produced a rapidly reversible blockade of SK channels as compared with apamin. The difference between the IC(50)s of apamin (0.45 nM) and methyl-laudanosine (1.8 microM) in SK3 cells was essentially due to a major difference in their k(-1) (0.028 s(-1) for apamin and >or=20 s(-1) for methyl-laudanosine). These experiments demonstrate that both methyl-laudanosine and methyl-noscapine are medium potency, quickly dissociating, SK channel blockers with a similar potency on the three SK subtypes. Methyl-noscapine may be superior in terms of specificity for the SK channels. [less ▲]

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See detailBases neurobiologiques et psychopharmacologiques
Scuvée-Moreau, Jacqueline ULg; Seutin, Vincent ULg; Van den Berghe, Marc

in Dierick, Michel; Ansseau, Marc; D'Haenen, Hugo (Eds.) et al Manuel de Psychopharmacothérapie (2003)

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See detailLa mesure du sentiment de compétence chez les aidants de patients déments
Vernooij-Dassen, M.; Kurz, Xavier; Scuvée-Moreau, Jacqueline ULg et al

in Revue épidémiologique Santé publique (2003), 51

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See detailA new approach to the qualitative evaluation of functional disability in dementia
Kurz, Xavier; Scuvée-Moreau, Jacqueline ULg; Rive, B. et al

in International Journal of Geriatric Psychiatry (2003), 18

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