Leanne Coyne

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Lacosamide (LCM) is anticonvulsant in animal models and is in phase 3 assessment for epilepsy and neuropathic pain. Here we seek to identify cellular actions for the new drug and effects on recognised target sites for anticonvulsant drugs. Radioligand binding and electrophysiology were used to study the effects of LCM at well-established mammalian targets(More)
Neurosteroids are modulators of several receptors and ion channels and are implicated in the pathophysiology of several neuropsychiatric diseases including hepatic encephalopathy (HE). The neurosteroid, allopregnanolone, a positive allosteric modulator of GABA(A) receptors, accumulates in the brains of HE patients where it can potentiate GABA(A)(More)
Anandamide is a prominent member of the endocannabinoids, a group of diffusible lipid molecules which influences neuronal excitability. In this context, endocannabinoids are known to modulate certain presynaptic Ca(2+) and K(+) channels, either through cannabinoid (CB1) receptor stimulation and second messenger pathway activation or by direct action. We(More)
Human pluripotent stem cells have enormous potential value in neuropharmacology and drug discovery yet there is little data on the major classes and properties of receptors and ion channels expressed by neurons derived from these stem cells. Recent studies in this lab have therefore used conventional patch-clamp electrophysiology to investigate the(More)
1. We examine the sensitivity of GABA(A) and glycine receptors (same ionotropic superfamily) to oleamide. We address subunit-dependence/modulatory mechanisms and analogies with depressant drugs. 2. Oleamide modulated human GABA(A) currents (alpha(1)beta(2)gamma(2L)) in oocytes (EC(50), 28.94+/-s.e.mean of 1.4 microM; Maximum 216%+/-35 of control, n=4).(More)
Fenamate NSAIDs have several central effects, including anti-epileptic and neuroprotective actions. The underlying mechanism(s) of these actions are not presently understood. In this study, the effects of five members of the fenamate NSAID group were investigated on native ligand-gated ion channels expressed in cultured rat hippocampal neurons. All(More)
Non-steroidal anti-inflammatory drugs (NSAIDs) have been used extensively in the treatment of inflammatory disorders and pain. In recent years, emerging data suggest that some NSAIDs possess pharmacological properties, in addition to cyclooxygenase inhibition, which may be beneficial in the treatment of several neurological conditions. For example, fenamate(More)
Expression of GEF1 in Xenopus laevis oocytes and HEK-293 cells gave rise to a Cl- channel that remained permanently open and was blocked by nitro-2-(3-phenyl-propylamino) benzoic acid and niflumic acid. NPPB induced petite-like colonies, resembling the GEF1 knock-out. The fluorescent halide indicator SPQ was quenched in a wild-type strain, in contrast to(More)
Resin acids from bleached wood pulp are toxic to fish. 12,14-Dichlorodehydroabietic acid (12,14-Cl(2)DHA) raises cytoplasmic Ca(2+) in synaptosomes and blocks neural GABA(A) receptors; however, the underlying mechanism remains unclear in these earlier rodent studies. 12,14-Cl(2)DHA (50μM) almost completely blocked native GABA(A) currents (rat cortical(More)
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