Trends in pharmacological sciences
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Trends Pharmacol. Sci. · Feb 2014
ReviewZebrafish as an emerging model for studying complex brain disorders.
The zebrafish (Danio rerio) is rapidly becoming a popular model organism in pharmacogenetics and neuropharmacology. Both larval and adult zebrafish are currently used to increase our understanding of brain function, dysfunction, and their genetic and pharmacological modulation. Here we review the developing utility of zebrafish in the analysis of complex brain disorders (including, e.g., depression, autism, psychoses, drug abuse, and cognitive deficits), also covering zebrafish applications towards the goal of modeling major human neuropsychiatric and drug-induced syndromes. We argue that zebrafish models of complex brain disorders and drug-induced conditions are a rapidly emerging critical field in translational neuroscience and pharmacology research.
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Trends Pharmacol. Sci. · Jan 2014
ReviewMolecularly targeted cancer therapy: some lessons from the past decade.
The tremendous advances achieved in the understanding of cancer biology have delivered unprecedented progress in molecularly targeted cancer therapy in the past decade. The fast growing category of targeted anticancer agents available for clinical use is accompanied by a conceptual revolution in anticancer drug development. ⋯ It is pivotal to take lessons from the past and seek new solutions. This review discusses conceptual progress and remaining challenges in molecularly targeted cancer therapy, and proposes feasible alternatives to increase chances of clinical success in the future.
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Making raw data from clinical trials widely publically available should reduce selective reporting biases and enhance the reproducibility of and trust in clinical research. The optimal procedures for data sharing are hotly debated. Some of the caveats and limitations in proposed data-sharing policies are potentially restrictive, and we argue in favor of more widespread availability of data from clinical research.
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Trends Pharmacol. Sci. · Jul 2013
ReviewNovel designer receptors to probe GPCR signaling and physiology.
Muscarinic receptor-based designer receptors have emerged as powerful novel tools to study G-protein-coupled receptor (GPCR) signaling and physiology. These new designer GPCRs, which are most frequently referred to as DREADDs (designer receptors exclusively activated by designer drug), are unable to bind acetylcholine, the endogenous muscarinic receptor agonist, but can be activated by clozapine-N-oxide (CNO), an otherwise pharmacologically inert compound, with high potency and efficacy. ⋯ The expression of DREADDs in distinct tissues or cell types has enabled researchers to study the outcome of selective stimulation of distinct GPCR (or arrestin) signaling pathways in a temporally and spatially controlled fashion in vivo. In this review, we provide an up-to-date snapshot of where this field currently stands and which important novel insights have been gained using this new technology.
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Trends Pharmacol. Sci. · Jun 2013
ReviewThe diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities?
Pregabalin is a specific ligand of the alpha2-delta (α2-δ) auxiliary subunit of voltage-gated calcium channels. A growing body of evidence from studies of anxiety and pain indicate that the observed responses with pregabalin may result from activity at the α2-δ auxiliary protein expressed presynaptically, in several different circuits of the central nervous system (CNS). ⋯ Whether this compound regulates synaptic function via α2-δ in additional conditions is yet to be discovered. The potential of pregabalin to regulate neuronal hyperactivity involving other CNS circuits will require further exploration.