Current pharmaceutical design
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With a constant focus on the primary tumor, the current approaches in drug development in oncology yield dismal results. However over 90 percent of cancer deaths today are due to metastasis formation and yet there is no anti-metastatic drug on the market. Tumor cell migration is the essential prerequisite for invasion and metastasis formation. ⋯ We provide an overview of currently available agonists and antagonists to these receptors, which have a potential as anti-metastatic targets. Moreover we provide with the example of beta-blockers, how established drugs in other indications are possibly effective and can be co-opted as such anti-metastatics. The increasing knowledge of such regulators opens new opportunities to target cancer spreading and may put forth the development of antimetastatic drugs for oncological therapy.
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Elevated serum uric acid (SUA) levels (i.e. hyperuricaemia) have been associated with metabolic syndrome (MetS) and cardiovascular disease (CVD) morbidity and mortality. Elevated SUA levels predict the onset of type 2 diabetes (T2DM). ⋯ The present review considers: (1) SUA levels in patients with MetS, type 1 diabetes and T2DM; (2) the mechanisms that influence SUA levels in these patients; (3) the potential links between SUA and diabetic complications. The effect on SUA levels of drugs commonly prescribed for T2DM and the risk of uric acid nephrolithiasis in patients with MetS or DM are also briefly discussed.
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Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. The major pathological consequences of IHD arise from the detrimental effects of acute ischemia-reperfusion injury (IRI) on the myocardium. ⋯ In this review article, we provide an overview of these endogenous cardioprotective strategies with respect to the pre-clinical experimental literature, exploring their major characteristics and underlying signaling mechanisms. The application of these therapeutic strategies in the clinical setting for potential patient benefit is reviewed in another article in this special issue.
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Pregabalin is an anticonvulsant drug that binds to the α₂δ (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness of pregabalin in its various fields of application. ⋯ Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases.
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γ-aminobutyric acid (GABA) plays many of its key roles in embryonic development and functioning of the central nervous system (CNS) by acting on ligand gated chloride-permeable channels known as GABAA receptors (GABAAR). Classically, GABAARmediated synaptic communication is tailored to allow rapid and precise transmission of information to synchronize the activity of large populations of cells to generate and maintain neuronal networks oscillations. An alternative type of inhibition mediated by GABAA receptors, initially described about 25 years ago, is characterized by a tonic activation of receptors that react to ambient extracellular GABA. ⋯ The molecular nature of the extrasynaptic GABAA receptors and the tonic inhibitory current they generate have been characterized in many brain structures, and due to its relevance in controlling neuron excitability they have become attractive pharmacological targets for a variety of neurological disorders such as schizophrenia, epilepsy and Parkinson disease. In the spinal cord, early studies have implicated these receptors in anesthesia, chronic pain, motor control, and locomotion. This review highlights past and present developments in the field of extrasynaptic GABAA receptors and emphasizes their subunit containing distribution and physiological role in the spinal cord.