Anticonvulsant activity of a novel NMDA/glycine site antagonist, MDL 104,653, against kindled and sound-induced seizures

Chapman, A. Chaston; Dürmüller, Niklaus; Harrison, Boyd L.; Baron, Bruce M.; Parvez, Naila; Meldrum, Brian S.

doi:10.1016/0014-2999(94)00713-h

Cited by 28 publications

(3 citation statements)

References 19 publications

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“…However, more recently some full glycineB antagonists with improved, but by no means optimal pharmacokinetic properties (Baron et al, 1992;Carling et al, 1993;Rowley et al, 1993;Woodward et al, 1995b) have also been reported to have good therapeutic indices following systemic administration as neuroprotective agents in models of focal ischaemia (Warner et al, 1995, Bordi et al, 1997 and trauma (Tsuchida and Bullock, 1995), as anti-epileptics, even in models of partial complex seizures (McCabe et al, 1993;Chapman et al, 1995;Smith et al, 1994), as anxiolytics (Kehne et al, 1995), as possible anti-psychotomimetics (Bristow et al, 1995(Bristow et al, , 1996, in blocking spreading depression (Obrenovitch and Zilka, 1996) and in models of hyperalgesia (Vaccarino et al, 1993;Millan and Seguin, 1994;Laird et al, 1996). This improved therapeutic profile may be due to the ability of full glycineB antagonists to reveal glycine-sensitive desensitization (Parsons et al, 1993).…”

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confidence: 97%

Modulation of NMDA receptors by glycine ? introduction to some basic aspects and recent developments

et al. 1998

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Glycine is a co-agonist at NMDA receptors and it's presence is a prerequisite for channel activation by glutamate or NMDA. Physiological concentrations reduce one form of NMDA receptor-desensitization. Interactions between the glycineB site and other domains of the NMDA receptor are complex and include the glutamate, Mg2+ and polyamines sites. Glycine shows different affinities at various NMDA receptor subtypes probably via to allosteric interactions between NMDA2 subunits and the glycine recognition site on the NMDAR1 subunit. There is still some debate whether the glycineB site is saturated in vivo but it seems likely that this depends on regional differences in receptor subtype expression, local glycine or D-serine concentrations and the expression of specific glycine transporters. GlycineB antagonists and partial agonists have been reported to have good therapeutic indices as neuroprotective agents against focal ischaemia and trauma, anti-epileptics, anxiolytics, anti-psychotomimetics and in models of chronic pain. They clearly lack two potentially serious side effects classically associated with NMDA receptor blockade, namely neurodegenerative changes in the cingulate/retrosplenial cortex and psychotomimetic-like effects. This improved therapeutic profile may be partially due to the ability of full glycineB antagonists to reveal glycine-sensitive desensitization and possibly also via functional and/or regional NMDA receptor subtype selectivity.

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confidence: 97%

Modulation of NMDA receptors by glycine ? introduction to some basic aspects and recent developments

et al. 1998

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“…A wide variety of compounds have been shown to compete with glycine at the glycineh-serine recognition site and to block NMDA-mediated excitation. Compounds of this kind that cross the bloodbrain barrier, such as L-687 414, ACEA 1021, and MDL 104653, are effective anticonvulsants in rodents and primates (61)(62).…”

Section: Glycine Site Nmda Antagonistsmentioning

confidence: 99%

Neurotransmission in Epilepsy

Meldrum¹

1995

Epilepsia

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Summary: Some evidence indicates that in some types of focal epilepsy the enhanced excitability is due in part to impaired γ‐aminobutyric acid (GABA)ergic inhibitory feedback. One form that this can take is impaired excitatory input to GABAergic interneurons. Enhanced excitatory receptor sensitivity, most characteristically involving N‐methyl‐D‐aspartate (NMDA) receptors, has been identified in kindled rodents and in focal epilepsy in humans. Drugs that enhance GABA‐mediated inhibition are anticonvulsant in many syndromes of generalized and focal epilepsy. Mechanisms through which this occurs include direct interaction with the GABAhenzodiazepine (BZD) receptor (BZDs, barbiturates, chlormethiazole), inhibition of GABA‐transaminase (vigabatrin, VGB) and blocking GABA uptake (tiagabine, TGB). Glutamate receptor antagonists (both NMDA and non‐NMDA antagonists) are potent anticonvulsants in many animal models of epilepsy. Whether pure glutamate receptor antagonists will have a clinical role as antiepileptic drugs (AEDs) remains to be established.

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“…Both have estrogenic action. 3 Viral-RNA polymerase Inhibitory action of few 4-hydroxyquinoline-2-one derivatives such as Compounds (III) and (IV) strongly prevent the replication of the Hepacivirus C. [4][5][6][7] In addition to this 4-Hydroxy-2(1H)quinolinones along with their derivatives are among the group of valuable heterocyclic compounds associated with many pharmacological, [8][9][10][11][12][13] various medicinal values such as analgesic, 14 anti-inflammatory, 15 diuretic, 16 antiallergenic, 17 orally active antagonists, 18 cardiovascular agents, 19 anticonvulsant, 20 antimicrobial (antibacterial and antifungal), [21][22][23] antitubercular, 24 dye-stuffs. 25 heating mantle, the reaction mixture in the alcohol is heated for three hours at refluxing temperature.…”

Section: Introductionmentioning

confidence: 99%

“Anti-microbial Study and Synthesis of Schiff bases of 3-actyl 4-hydroxy Quinolin-2-one”

Anjanikar¹,

Chandole

2023

Orient. J. Chem

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Quinoline based new Schiff bases were synthesized from 3-Actyl 4-Hydroxy Quinolin-2-(1H)-one and screened their antibacterial and antifungal activity. The Schiff bases 4-hydroxy-3-(1-((4-picolin-2-yl)imino)ethyl)quinolin-2-(1H)-one(L1),4-hydroxy-3-(1-((5-picolin-2-yl)imino)ethyl)quinolin-2(1H)-one(L2),4-hydroxy-3-(1-((6-picolin-2-yl)-imino)ethyl)quinolin-2(1H)-one(L3) and 4-hydroxy-3-(1-((3-nitro-4-picolin-2-yl)imino)ethyl)quinolin-2-(1H)-one (L4) were preparedfrom 3-Acetyl 4-Hydroxy Quinolin-2-One with 2-amino picolines. The structures of Schiff bases were confirmed by Infrared, mass, proton-NMR and 13CNMR spectral analysis. In vitro studies of these Schiff bases were carried out for their antibacterial activity by Agar contact method and antifungal activity by the poison plate method. The bacterial species used were B. subtilis, E. coli, S. typhi, and S. aureus. Fungal species used were F. moneliforme, A.niger, A. flavus, and P. chrysogenum.

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Anticonvulsant activity of a novel NMDA/glycine site antagonist, MDL 104,653, against kindled and sound-induced seizures

Cited by 28 publications

References 19 publications

Modulation of NMDA receptors by glycine ? introduction to some basic aspects and recent developments

Modulation of NMDA receptors by glycine ? introduction to some basic aspects and recent developments

Neurotransmission in Epilepsy

“Anti-microbial Study and Synthesis of Schiff bases of 3-actyl 4-hydroxy Quinolin-2-one”

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