Marc Williams Debono

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In this paper, we report on the pharmacological and functional profile of SSR180711 (1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic acid, 4-bromophenyl ester), a new selective alpha7 acetylcholine nicotinic receptor (n-AChRs) partial agonist. SSR180711 displays high affinity for rat and human alpha7 n-AChRs (K(i) of 22+/-4 and 14+/-1 nM, respectively). Ex vivo(More)
The development of the synaptic responses of intracerebellar nuclei neurons was studied in the rat by the use of thick sagittal cerebellar slices maintained in vitro. It has been shown that functional excitatory synapses are present on these neurons from birth, probably due to climbing and/or mossy fiber collaterals; functional inhibitory synapses, due to(More)
The development of membrane conductances of intracerebellar nuclei neurons was studied in the rat since birth up to the weaning period by the use of thick sagittal cerebellar slices maintained in vitro. Mature nuclear neurons express fast sodium and slowly inactivating sodium conductances, as well as calcium conductances. As early as birth, fast sodium and(More)
Excessive release of glutamate, a potent excitatory neurotransmitter, is thought to play an important role in a variety of acute and chronic neurological disorders, suggesting that excitatory amino acid antagonists may have broad therapeutic potential in neurology. Here, we describe the synthesis, pharmacological properties and neuroprotective activity of(More)
The effects of riluzole, an anticonvulsant and neuroprotective compound, on excitatory amino acid-evoked currents were studied in Xenopus laevis oocytes injected with mRNA from rat whole brain or cortex. Responses to kainic acid were blocked by riluzole (IC50 = 167 microM) as well as by the quinoxalinedione antagonists 6-cyano-7-nitroquinoxaline-2,3-dione(More)
Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonists are of potential interest for the treatment of certain acute and chronic neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we describe the synthesis and pharmacological properties of(More)
1. The effects of the alpha 2-adrenergic agonist clonidine on the membrane properties of Purkinje cells were analysed in sagittal slices of adult rat cerebellum by the use of intracellular recordings performed at a somatic level in the single-electrode voltage-clamp mode. 2. In preliminary current-clamp experiments, clonidine elicited in all cells a(More)
The overstimulation of excitatory amino acid receptors such as the glutamate AMPA receptor has been implicated in the physiopathogenesis of epilepsy as well as in acute and chronic neurodegenerative disorders. An original series of readily water soluble 4-oxo-10-substituted-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives was synthesized.(More)
A novel series of 2-substituted-4,5-dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazine derivatives was synthesised. One of them, 4e-a highly water soluble compound exhibited a nanomolar affinity and demonstrated competitive antagonist properties at the ionotropic AMPA receptors. This compound also displayed potent anticonvulsant properties against(More)