References of "Scuvée-Moreau, Jacqueline"
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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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See detailModulation of small conductance calcium-activated potassium (SK) channels: a new challenge in medicinal chemistry.
Liégeois, Jean-François ULg; Mercier, Frédéric ULg; Graulich, Amaury et al

in Current Medicinal Chemistry (2003), 10(8), 625-47

Small conductance calcium-activated potassium (SK) channels are found in many types of neurons as well as in some other cell types. These channels are selective for K(+) and open when intracellular Ca(2 ... [more ▼]

Small conductance calcium-activated potassium (SK) channels are found in many types of neurons as well as in some other cell types. These channels are selective for K(+) and open when intracellular Ca(2+) rises to omega 500 nM. In neurons, this occurs during and after an action potential. Activation of SK channels hyperpolarizes the membrane, thus reducing cell excitability for several tens or hundreds of milliseconds. This phenomenon is called a afterhyperpolarization (AHP). Three subtypes of SK channels (SK1, SK2, SK3) have been cloned and exhibit a differential localization in the brain. SK channels may play a role in physiological and pathological conditions. They may be involved in the control of memory and cognition. Moreover, they are heavily expressed in the basal ganglia (in particular in the substantia nigra, pars compacta) and in the limbic system, suggesting that they may modulate motricity and emotional behaviour. Based on these facts, SK channel subtypes may be a suitable target for developing novel therapeutic agents, but more work is needed to validate these targets. Hence, there is a great need for selective ligands. Moreover, although the risk of peripheral side-effects for SK channel modulators appears to be low, some questions remain to be investigated. Currently, different molecules are known as SK channel modulators. Apamin is a very potent peptidic agent; it produces a strong blockade of these targets which is only very slowly reversible and it has limited selectivity. Dequalinium was found to be an effective blocker. Different chemical modulations on the dequalinium structure led to the discovery of highly potent bis-quinolinium derivatives such as UCL 1684. Other bis-(2-amino-benzimidazole) derivatives are in development. On the other hand, quaternary salts of bicuculline were reported to be effective in inhibiting AHPs. More recent developments on structurally-related molecules revealed that methyl-laudanosine is a new interesting tool for exploring SK channel pharmacology. Finally, a family of compounds has been shown to facilitate SK channel opening. Such compounds may be useful in treating disorders involving neuronal hyperexcitability. [less ▲]

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See detailCognitive impairment, dementia and quality of life.
Kurz, Xavier; Scuvée-Moreau, Jacqueline ULg; Vernooij-Dassen, M. et al

in Acta Neurologica Belgica (2003), 103

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See detailMethyl-laudanosine: A new pharmacological tool to investigate the function of small-conductance Ca2+-activated K+ channels
Scuvée-Moreau, Jacqueline ULg; Liégeois, Jean-François ULg; Massotte, Laurent ULg et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2002), 302(3), 1176-1183

Small-conductance Ca(2+)-activated K(+) channels (SK channels) underlie the prolonged postspike afterhyperpolarization (AHP) observed in many central neurons and play an important role in modulating ... [more ▼]

Small-conductance Ca(2+)-activated K(+) channels (SK channels) underlie the prolonged postspike afterhyperpolarization (AHP) observed in many central neurons and play an important role in modulating neuronal activity. However, a lack of specific and reversible blockers of these channels hampers their study in various experimental conditions. Because previous work has shown that bicuculline salts block these channels, we examined whether related alkaloids, namely laudanosine quaternary derivatives, would produce similar effects. Intracellular recordings were performed on rat midbrain dopaminergic neurons and hippocampus CA1 pyramidal cells. Binding experiments were performed on rat cerebral cortex membranes. Laudanosine, methyl-laudanosine, and ethyl-laudanosine blocked the apamin-sensitive AHP of dopaminergic neurons with mean IC(50) values of 152, 15, and 47 microM, respectively. The benzyl and butyl derivatives were less potent. Methyl-laudanosine had no effect on the I(h) current, action potential parameters, or membrane resistance of dopaminergic cells, or on the decrease in input resistance induced by muscimol, indicating a lack of antagonism at GABA(A) receptors. Interestingly, 100 microM methyl-laudanosine induced a significant increase in spiking frequency of dopaminergic neurons but not of CA1 pyramidal cells, suggesting the possibility of regional selectivity. Binding experiments on laudanosine derivatives were in good agreement with electrophysiological data. Moreover, methyl-laudanosine has no affinity for voltage-gated potassium channels, and its affinity for SK channels (IC(50) 4 microM) is superior to its affinity for muscarinic (IC(50) 114 microM) and neuronal nicotinic (IC(50) > or =367 microM) receptors. Methyl-laudanosine may be a valuable pharmacological tool to investigate the role of SK channels in various experimental models. [less ▲]

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See detailProgres recents dans la pharmacologie des hypnotiques et anxiolytiques
Scuvée-Moreau, Jacqueline ULg; Seutin, Vincent ULg

in Revue Médicale de Liège (2001), 56(3), 159-64

Recent studies on the respective contribution of GABAA receptor subunits in the various pharmacological effects of benzodiazepines suggest that the sedative and amnesic properties of diazepam are mediated ... [more ▼]

Recent studies on the respective contribution of GABAA receptor subunits in the various pharmacological effects of benzodiazepines suggest that the sedative and amnesic properties of diazepam are mediated by enhancement of gabaergic transmission in neurons expressing the alpha 1 subunit while the anxiolytic effect is selectively mediated by alpha 2 subunit. These findings suggest that a separation of the pharmacological properties of benzodiazepines is possible and that drugs with increased clinical specificity could be developed. [less ▲]

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See detailMethodological Issues in a Cost-of-Dementia Study in Belgium: The National Dementia Economic Study (Nades)
Kurz, Xavier; Broers, Mattie; Scuvée-Moreau, Jacqueline ULg et al

in Acta Neurologica Belgica (1999), 99(3), 167-75

The NAtional Dementia Economic Study (NADES) is an on-going prospective, one-year cohort study developed in Belgium to assess the socio-economic consequences of dementia in a group of patients and their ... [more ▼]

The NAtional Dementia Economic Study (NADES) is an on-going prospective, one-year cohort study developed in Belgium to assess the socio-economic consequences of dementia in a group of patients and their caregivers (n = 400). Comparison is made with a group of subjects with cognitive impairment and no dementia (n = 100) and a group of subjects without any cognitive impairment (n = 100). Recruitment of subjects is based on screening of warning signs of dementia by general practitioners, followed by a Cambridge Mental Disorders of the Elderly Examination (CAMDEX) performed at home. This paper presents an overview of the study protocol and the rationale for basic design options, such as the choice of study population, screening strategy, and methods used for the case validation. It also presents preliminary results on the prevalence of dementia in general practice, the sensitivity and specificity of the warning signs as a screening test of dementia, and the validity of a computerised case ascertainment algorithm based on DSM-III-R criteria. [less ▲]

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See detailSpontaneous Apamin-Sensitive Hyperpolarizations in Dopaminergic Neurons of Neonatal Rats
Seutin, Vincent ULg; Massotte, Laurent ULg; Scuvée-Moreau, Jacqueline ULg et al

in Journal of Neurophysiology (1998), 80(6), 3361-4

Spontaneous apamin-sensitive hyperpolarizations in dopaminergic neurons of neonatal rats. J. Neurophysiol. 80: 3361-3364, 1998. Intracellular recordings from substantia nigra slices revealed the existence ... [more ▼]

Spontaneous apamin-sensitive hyperpolarizations in dopaminergic neurons of neonatal rats. J. Neurophysiol. 80: 3361-3364, 1998. Intracellular recordings from substantia nigra slices revealed the existence of spontaneous hyperpolarizations (amplitude 2-8 mV, duration 100-400 ms) at -60 mV in most dopaminergic neurons of neonatal (9-15 days) but not adult rats. These events were blocked by apamin (300 nM) and bicuculline methochloride (100-300 microM), which blocks apamin-sensitive currents. They were unaffected by the selective gamma-aminobutyric acid-A (GABAA) antagonists SR95531 (100 microM) and picrotoxin (30-50 microM), the GABAB antagonist CGP35348 (300 microM), the D2 antagonist haloperidol (1 microM), and the metabotropic antagonist MCPG (1 mM). The hyperpolarizations were strongly attenuated or abolished when recording electrodes contained 200 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. They were resistant to tetrodotoxin in the majority of the cells. They had some voltage dependency and were in some cases transiently potentiated when cells were briefly depolarized by current injection. We conclude that dopaminergic neurons have developmentally regulated physiological properties. These spontaneous hyperpolarizations might affect the firing rate of these cells, which was found to be lower in neonates than in adults. [less ▲]

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See detailEffect of potassium channel openers on the firing rate of hippocampal pyramidal cells and A10 dopaminergic neurons in vitro.
Scuvée-Moreau, Jacqueline ULg; Seutin, Vincent ULg; Vrijens, Bernard ULg et al

in Archives of Physiology & Biochemistry (1997), 105(5), 421-8

The effect of four KATP channel openers (KCOs) on the firing rate of CA1 pyramidal cells and A10 dopaminergic neurons was investigated using extracellular recording techniques in rat brain slices ... [more ▼]

The effect of four KATP channel openers (KCOs) on the firing rate of CA1 pyramidal cells and A10 dopaminergic neurons was investigated using extracellular recording techniques in rat brain slices. Pinacidil, lemakalim, diazoxide and a new compound, BPDZ44, had an inhibitory effect on the electrical activity of CA1 pyramidal cells. They all had a similar potency. Only BPDZ44 and diazoxide inhibited the firing rate of A10 dopamine neurons. The sulfonylurea glipizide (1 microM) antagonized the effect of BPDZ44 and diazoxide on A10 neurons but failed to antagonize the effect of KCOs on CA1 pyramidal cells. These results show that differences exist among KCOs in their ability to decrease the electrical activity of various populations of central neurons. [less ▲]

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See detailEvidence for a Non-Gabaergic Action of Quaternary Salts of Bicuculline on Dopaminergic Neurones
Seutin, Vincent ULg; Scuvée-Moreau, Jacqueline ULg; Dresse, Albert ULg

in Neuropharmacology (1997), 36(11-12, Nov-Dec), 1653-7

Intracellular recordings were made from neurones, presumed to be dopaminergic, in the rat midbrain slice preparation. Bicuculline methiodide (BMI) and methochloride (BMC) reversibly blocked the slow ... [more ▼]

Intracellular recordings were made from neurones, presumed to be dopaminergic, in the rat midbrain slice preparation. Bicuculline methiodide (BMI) and methochloride (BMC) reversibly blocked the slow, apamin-sensitive component of the afterhyperpolarization in these cells. The IC50 for this effect was about 26 microM. In comparison, BMC antagonized the input resistance decrease evoked by muscimol (3 microM) with an IC50 of 7 microM. The base of bicuculline was less potent in blocking the slow afterhyperpolarization. SR95531 (2-[carboxy-3'-propyl]-3-amino-6-paramethoxy-phenyl-pyridaziniu m bromide), another competitive GABA(A) antagonist, and picrotoxin, a non-competitive GABA(A) antagonist, also blocked the action of muscimol (IC50s: 2 and 12 microM respectively), but had no effect on the afterhyperpolarization at a concentration of up to 100 microM. Moreover, 100 microM SR95531 did not affect the blockade of the afterhyperpolarization by BMC. This blockade persisted in the presence of tetrodotoxin and was apparently not due to a reduction of calcium entry, suggesting that it involved a direct action on the channels which mediate this afterhyperpolarization. These results strongly suggest that quaternary salts of bicuculline act on more than one target in the central nervous system. Thus, the involvement of GABA(A) receptors in a given effect cannot be proven solely on the basis of its blockade by these agents. [less ▲]

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See detailHydrogen Peroxide Hyperpolarizes Rat Ca1 Pyramidal Neurons by Inducing an Increase in Potassium Conductance
Seutin, Vincent ULg; Scuvée-Moreau, Jacqueline ULg; Massotte, Laurent ULg et al

in Brain Research (1995), 683(2), 275-8

It has been suggested that hydrogen peroxide is involved in cascades of pathological events affecting neural cells. The aim of this study was therefore to examine whether this molecule is able by itself ... [more ▼]

It has been suggested that hydrogen peroxide is involved in cascades of pathological events affecting neural cells. The aim of this study was therefore to examine whether this molecule is able by itself to modify membrane properties of pyramidal neurons in the CA1 region of the rat hippocampus. Intracellular recordings in the slice preparation showed that 3.3 mM hydrogen peroxide hyperpolarized all neurons tested (n = 41) by 11 +/- 3 mV. This effect persisted in the presence of tetrodotoxin. It developed slowly, was reversible and reproducible. In the presence of tetrodotoxin, the extrapolated reversal potential of this effect was -95 +/- 5 mV in 2.5 mM external potassium. This value was not significantly different from the one obtained with the GABAB agonist baclofen (10 microM) (-98 +/- 5 mV). It shifted when the concentration of external potassium was increased to 10.5 mM (from -96 +/- 5 to -62 +/- 4 mV), in close agreement with the Nernst equation potassium ions. The hyperpolarization was significantly reduced (by 65 +/- 22%) by the potassium channel blocker barium (100 microM). We suggest that hydrogen peroxide is able to induce an increase in potassium conductance in rat CA1 pyramidal neurons. The exact mechanism by which it produces this effect (direct action on channels or indirect effect) remains to be determined. [less ▲]

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