Clinical Pharmacology of Sulfonylureas

Groop, Leif; Neugebauer, G

doi:10.1007/978-3-662-09127-2_9

Cited by 6 publications

(4 citation statements)

References 323 publications

(313 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sulphonylureas like glibenclamide stimulate insulin secretion and are used as treatment in type‐2 diabetes (Groop & Neugebauer, 1996). At higher concentrations glibenclamide shows effects also in the ischaemic heart, where it blocks the ischaemia‐induced narrowing of the cardiac action potential (Fosset et al ., 1988) and the dilatation of the coronary vascular bed (Daut et al ., 1990).…”

Section: Introductionmentioning

confidence: 99%

Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides

Hambrock

Löffler-Walz

Quast

2002

British J Pharmacology

View full text Add to dashboard Cite

1 ATP-sensitive K + channels are composed of pore-forming subunits Kir6.2 and of sulphonylurea receptors (SURs); the latter are the target of the hypoglycaemic sulphonylureas like glibenclamide. Here, we report on the negative allosteric modulation by MgATP and MgADP of glibenclamide binding to SUR1 and to SUR2 mutants with high glibenclamide anity, SUR2A(Y1206S) and SUR2B(Y1206S). 2 ATP, in the presence of an ATP-regenerating system to oppose hydrolysis during incubation, inhibited glibenclamide binding to SUR1 and SUR2B(Y1206S) by *60%, to SUR2A(Y1206S) by 21%). Inhibition curves for the SUR2(Y1206S) isoforms were monophasic with IC 50 values of 5 ± 10 mM; the curve for SUR1 was biphasic (IC 50 values 4.7 and 1300 mM). 3 Glibenclamide inhibition curves for ADP, performed in the presence of an ATP-consuming system to oppose ATP formation from ADP, were generally shifted rightwards and showed positive cooperativity, in particular with the SUR2(Y1206S) isoforms. 4 In the absence of the coupled enzyme systems, inhibition curves of MgATP or MgADP were generally shifted leftwards. This indicated synergy of MgATP and MgATP in acting together. 5 Coexpression of SUR1 and SUR2B(Y1206S) with Kir6.2 reduced both potency and ecacy of ATP in inhibiting glibenclamide binding; this was particularly marked for Kir6.2/SUR1. 6 The data show (a) that the inhibitory eects of ATP and ADP on glibenclamide binding dier from one another, (b) that they depend on the SUR subtype, and (c) that they are weakened by coexpression with Kir6.2.

show abstract

Section: Introductionmentioning

confidence: 99%

Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides

Hambrock

Löffler-Walz

Quast

2002

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Aliphatic and aromatic substituents on sulfonylthiourea moieties act as lipophilic centers essential for agonistic action on SUR. Furthermore, the sulfamoyl NH group is completely ionized at physiological pH due to its acidity (pKa = 4.9-6.5) [61]. This ionization provides the anionic linker that is markedly required for SUR agonists [62].…”

Section: As Antidiabetic Agentsmentioning

confidence: 99%

Design, Molecular Docking, Synthesis, Anticancer and Anti-Hyperglycemic Assessments of Thiazolidine-2,4-diones Bearing Sulfonylthiourea Moieties as Potent VEGFR-2 Inhibitors and PPARγ Agonists

et al. 2022

View full text Add to dashboard Cite

Newly designed thiazolidine-2,4-diones 3–7a–c were synthesized, and their anticancer activities were screened against three cancer lines. They showed potent activities against HepG2 compared to the other HCT116 and MCF-7 tumor cell lines. Compounds 7c and 6c were detected as highly effective derivatives against MCF-7 (IC50 = 7.78 and 8.15 µM), HCT116 (IC50 = 5.77 and 7.11 µM) and HepG2 (IC50 = 8.82 and 8.99 µM). The highly effective derivatives 6a–c and 7a–c were tested against VERO normal cell lines. All derivatives were evaluated for their VEGFR-2 inhibitory actions and demonstrated high to low activities, with IC50 values varying from 0.08 to 0.93 µM. Moreover, derivatives 5a–c, 6a–c and 7a–c were assessed to verify their in vitro binding affinities to PPARγ and insulin-secreting activities. Finally, docking studies were performed to explore their affinities and binding modes toward both VEGFR-2 and PPARγ receptors.

show abstract

“…Non-selective beta-adrenergic blockers such as propronolol, nadolol, etc. potentiate the hypoglycemic effects of sulfonylureas through the inhibition of glycogenolysis, gluconeogenesis and lipolysis and the stimulation of glucose uptake (Aziz et al, 1996;Groop, Neugebauer, 1996;Gaafar et al, 1994). Cardioselective beta blockers such as atenolol, metoprolol, etc.…”

Section: Beta-adrenergic Blockersmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Interactions of Sulfonylurea Antidiabetics

2018

European Journal of Medicine

View full text Add to dashboard Cite

Sulfonylureas are useful to treat type 2 diabetes patients. Apart from sulfonylureas, the patients with diabetes may use many other medications to treat various concomitant illnesses such as high blood pressure, higher lipids, infections, pain, etc. The probability of interactions increases with the number of drugs used concomitantly. Most of the adverse drug interactions of sulfonylureas result in hypoglycemia, which can be life threatening. Sulfonylureas are primarily metabolized by CYP2C9 enzyme, which paves the way for most of their pharmacokinetic drug interactions. Drugs inhibiting CYP2C9 enzyme are expected to elevate the plasma concentrations of sulfonylureas and subsequent hypoglycemic complications. Some drugs potentiate the hypoglycemic activity of sulfonylureas pharmacodynamically too. The prescribers and pharmacists must be aware of the adverse drug interactions of sulfonylureas to prevent hypoglycemic episodes.

show abstract

Clinical Pharmacology of Sulfonylureas

Cited by 6 publications

References 323 publications

Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides

Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides

Design, Molecular Docking, Synthesis, Anticancer and Anti-Hyperglycemic Assessments of Thiazolidine-2,4-diones Bearing Sulfonylthiourea Moieties as Potent VEGFR-2 Inhibitors and PPARγ Agonists

Pharmacokinetic and Pharmacodynamic Interactions of Sulfonylurea Antidiabetics

Contact Info

Product

Resources

About