Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The classic centrally acting antihypertensives such as clonidine, guanfacine and alpha-methyl-DOPA (via its active metabolite alpha-methyl-noradrenaline) induce peripheral sympathoinhibition and a fall in blood pressure as a result of alpha2-adrenoceptor stimulation in the brain stem. These drugs have lost much of their clinical importance because of their unfavourable side-effects (sedation, dry mouth, impotence), which are also mediated by alpha2-adrenoceptors, although in other anatomical regions. Moxonidine and rilmenidine are the examples of a new class of centrally acting antihypertensives, which cause peripheral sympathoinhibition mediated by imidazoline (I1)-receptors in the rostral ventromedulla (RVLM). Their side-effect profile appears to be better than that of clonidine and alpha-methyl-DOPA, probably because of a weaker affinity for alpha2-adrenoceptors. The mode of action, haemodynamic profile, antihypertensive efficacy and adverse reactions of the classic and newer centrally acting antihypertensives are the subject of the present survey. Attention is also paid to other therapeutic applications of centrally acting antihypertensives, such as congestive heart failure and the metabolic syndrome.
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PMID:Centrally acting antihypertensive drugs. Present and future. 1042 8

Central imidazoline (I(1))-receptors have been recognised as targets of a new class of centrally acting antihypertensives. The stimulation of these I(1)-receptors induces peripheral sympatho-inhibition and a reduction of (elevated) blood pressure. Moxonidine and rilmenidine are the prototypes of this new class of centrally acting antihypertensives. These imidazoline receptor stimulants are effective antihypertensives with a haemodynamic profile which is attractive from a pathophysiological point of view. Since both moxonidine and rilmenidine have a much weaker affinity for central (2)-adrenoceptors than classic centrally acting drugs, for example, clonidine and alpha-methyl-DOPA, the side-effects profile of the I(1)-receptor stimulants is significantly better. The imidazoline (I(1))-receptor stimulants are the subject of the current survey. They appear to offer the possibility of developing centrally acting antihypertensives with the same attractive haemodynamic characteristics as the classic alpha(2)-adrenoceptor stimulants, but with clearly better tolerability. Their potential use in the treatment of congestive heart failure and the metabolic syndrome is subject to clinical investigation.
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PMID:Antihypertensive drugs interacting with central imidazoline (I1)-receptors. 1599 29

Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context.
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PMID:Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila. 2653 Apr 16