Rachael M Nelson

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Simulated ischemic conditions (hypoxia-hypoglycaemia) in vitro enhanced glutamate efflux from rat cerebrocortical prisms. Here we characterised efflux mechanisms using pharmacological tools. The Na(+) channel blocker TTX (1 microM) did not affect ischemia-induced efflux, while sipatrigine (100 microM), a Na(+)/Ca(2+) channel blocker and omega-conotoxin(More)
Prisms of adult rat cortex were maintained in vitro in either aerobic conditions (control) or conditions simulating an acute ischaemic challenge (hypoxia with no added glucose). Endogenous glutamate efflux increased with time in ischaemic conditions, being 2.7 fold higher than control efflux at 45 min. Returning prisms to control solution after 20 min of(More)
Clomethiazole is a gamma-aminobutyric acid (GABA)-mimetic agent with anticonvulsant, sedative and neuroprotective properties. The pharmacological actions of clomethiazole that underlie its functional profile have not been fully explored, but are known to result from an interaction with the GABA(A) receptor. Here, we present a quantitative(More)
We have investigated the neuroprotective properties of AR-A008055 [(+/-)-1-(4-methyl-5-thiazolyl-1-phenyl-methylamine], a novel compound structurally related to clomethiazole. Administration (i.p.) of (+/-)-AR-A008055 60 min after 5 min of global cerebral ischaemia in gerbils produced a dose-dependent protection of the hippocampus from damage. Both(More)
Nociceptin/orphanin FQ (NC), the endogenous ligand for the G-protein coupled nociceptin receptor (NCR), has a modulatory role in various physiological processes including neurotransmitter release. We have examined the effects of NC, the analogues NC(1-13)NH2 and [F/G]NC(1-13)NH2 and the competitive antagonist [Nphe1]NC(1-13)NH2 (Nphe1) on glutamate efflux(More)
We tested whether glutamate receptor ligands affect oxygen-glucose deprivation-evoked L-glutamate efflux from adult rat cerebrocortical prisms. The uncompetitive NMDA antagonist AR-R15896AR inhibited efflux (IC50 34 microM, 87% maximal inhibition). AMPA/kainate receptor blockade (NBQX, 100 microM) or Group II metabotropic glutamate receptor activation(More)
AR-A008055 [(+/-)-1-(4-methyl-5-thiazolyl)-1-phenylmethylamine] is structurally related to clomethiazole and has been used to probe the mechanism of the neuroprotective effect of clomethiazole. Clomethiazole, (+/-)-AR-A008055 and (S)-(-)-AR-A008055 all displaced [35S]-t-butyl-bicyclophosphorothionate ([35S]TBPS) from rat cerebral cortex tissue (IC50 values:(More)
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