Drugs Acting on Multiple Receptors: β-Blockers with Additional Properties

Sponer, G.; Bartsch, W.; Hooper, Robert G.

doi:10.1007/978-3-642-74209-5_5

Cited by 8 publications

(4 citation statements)

References 313 publications

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“…We chose the drug with a relatively simple withdrawal area because that made it easy to locate the population. Dilevalol was finally chosen because it was only withdrawn in England [ 30 ]. Dilevalol is the (R, R)-isomer of the approved drug Labetalol.…”

Section: Methodsmentioning

confidence: 99%

Prediction on the risk population of idiosyncratic adverse reactions based on molecular docking with mutant proteins

et al. 2017

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Idiosyncratic adverse drug reactions are drug reactions that occur rarely and unpredictably among the population. These reactions often occur after a drug is marketed, which means that they are strongly related to the genotype of the population. The prediction of such adverse reactions is a major challenge because of the lack of appropriate test models during the drug development process. In this study, we chose withdrawn drugs because the reasons why they were withdrawn and from which countries or regions is easily obtained. We selected Dilevalol and its chiral drug (Labetalol) as the investigatory drugs, as they have been withdrawn from a European market (Britain) because of serious hepatotoxicity. First, we searched for and obtained the Dilevalol-induced- liver-injury related protein, multidrug resistance protein 1 (MDR1), from the Comparative Toxicogenomics Database (CTD). Then, we searched and extracted 477 non-synonymous single nucleotide polymorphisms (nsSNP) on MDR1 in the dbSNP database. Second, we used the VarMod tool to predict the functional changes of MDR1 induced by these nsSNPs, from which we extracted the nsSNPs that significantly change the functions of this protein. Third, we built the three-dimensional structures of those variant proteins and used AutoDock to perform a docking study, choosing the best model to determine the sites of nsSNPs. Finally, we used the data from the 1000 Genomes Project to verify the dominant population distribution of the risk SNP. We applied the same strategy to the post-marketing drug-induced liver injury drugs to further test the feasibility of our method.

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Section: Methodsmentioning

confidence: 99%

Prediction on the risk population of idiosyncratic adverse reactions based on molecular docking with mutant proteins

et al. 2017

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“…Carvedilol, (±)-1-(carbazol-4-yloxy)-3-((2-(o-methoxyphenoxy)ethyl)amino)-2-propanol, is a nonselective ␤-blocking agent [1][2], which also has vasodilating properties that are mainly attributed to its blocking activity at ␣ 1 -receptors [3]. Carvedilol is used in the treatment of mild to moderate hypertension [4][5] and angina pectoris [6], and is often used in combination with other drugs.…”

Section: Introductionmentioning

confidence: 99%

Gas chromatograph–mass spectrometric method for the determination of carvedilol and its metabolites in human urine

Myung

2005

Journal of Chromatography B

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“…Labetalol [2,18] was the first fi-adrenergicblocking drug developed which in addition to P-receptor blockade possessed a peripheral vasodilating action: but more recently other 35 agents have been described [ 19,20]. There are three possible mechanisms for their dilating action, an a-blocking action, a P^-mediated vasodilation and a vasodilating action inde pendent of either the a-or P-receptors.…”

Section: Combined-action Beta-blocking Drugsmentioning

confidence: 99%

Carvedilol in Ischaemic Heart Disease

Prichard

1993

Cardiology

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β-adrenoceptor-blocking drugs, first introduced for the treatment of symptomatic angina pectoris, have been found effective across the whole spectrum of ischaemic disease. Labetalol was the first combined-action beta-blocking drug to be described and was shown to be capable of increasing exercise tolerance in patients with angina pectoris. Carvedilol also possesses a peripheral vasodilating action mainly due to an α₁- adrenoceptor blockade. Haemodynamic studies with carvedilol in patients with ischaemic heart disease have shown a reduction in peripheral vascular resistance in contrast to propranolol which increases systemic resistance and reduces cardiac output. Additionally, in ischaemic heart failure there is evidence of improved myocardial function, as shown by an increase in ejection fraction, after the administration of carvedilol. Carvedilol has been shown to improve exercise tolerance in patients with angina pectoris and reduce the occurrence of episodes of silent myocardial ischaemia. Carvedilol, unlike many beta-blocking drugs, does not adversely affect the plasma lipid profile qualitatively or quantitatively. In contrast to many non-selective beta-blocking drugs, carvedilol has a more favourable haemodynamic profile, and its lack of adverse influence on the plasma lipid profile may be important in its long-term use.

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Drugs Acting on Multiple Receptors: β-Blockers with Additional Properties

Cited by 8 publications

References 313 publications

Prediction on the risk population of idiosyncratic adverse reactions based on molecular docking with mutant proteins

Prediction on the risk population of idiosyncratic adverse reactions based on molecular docking with mutant proteins

Gas chromatograph–mass spectrometric method for the determination of carvedilol and its metabolites in human urine

Carvedilol in Ischaemic Heart Disease

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