Diuretic Action of Three Sulfonylurea Drugs

Moses, Arnold M.; Howanitz, Joan H.; Miller, Myron

doi:10.7326/0003-4819-78-4-541

Cited by 72 publications

(23 citation statements)

References 17 publications

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“…Finally, two different sulfonylureas, CPMD and glyburide (24), both inhibited PG synthesis and potentiated the effect of VP in urinary bladder in vitro in an identical way (24). However, in contrast to CPMD, glyburide (8,(25)(26)(27) does not potentiate VP and rather causes diuresis in man and in experimental animals (8,(25)(26)(27). All these considerations suggest that, unlike in amphibians in vitro, the inhibition of PG synthesis is not a basis of CPMD actions on mammalian kidney observed in vivo.…”

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confidence: 98%

“…First, it has been difficult to explain why not only CPMD but also some other sulfonylurea antidiabetic drugs, namely glyburide, which do not have VP-enhancing properties in mammalian kidney in vivo (8,(25)(26)(27), also inhibited the PGE2 synthesis and enhanced VP-induced water flow in the amphibian bladder system in vitro in a way similar to CPMD (8,24). Also, it appears puzzling that treatment of rats with CPMD either does not diminish (28), but even enhances (18) (12,(29)(30)(31).…”

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“…The question naturally arises whether renal effects of CPMD may be a consequence of its action on insulin secretion and hypoglycemia. Sulfonylureas other than CPMD, i.e., tolazamide, glyburide, and acetohexamide have hypoglycemic and other metabolic effects analogous to CPMD, but these compounds do not enhance VP-induced antidiuresis; on the contrary, they are diuretic in DI rats and DI men (8,(25)(26)(27). These comparisons argue strongly, albeit indirectly, against the notion that hypoglycemic action of CPMD is the basis of the observed renal effects.…”

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Chlorpropamide action on renal concentrating mechanism in rats with hypothalamic diabetes insipidus.

Kusano¹,

Braun-Werness²,

Vick³

et al. 1983

J. Clin. Invest.

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A B S T R A C T To determine vasopressin (VP)-potentiating effect of chlorpropamide (CPMD), we studied the effect of CPMD in vivo and in vitro in kidneys and in specific tubule segments of rats with hypothalamic diabetes insipidus, homozygotes of the Brattleboro strain (DI rats). Rats on ad lib. water intake were treated with CPMD (20 mg/100 g body wt s.c. daily) for 7 d. While on ad lib. water intake, the urine flow, urine osmolality, urinary excretion of Na+, K+, creatinine, or total solute excretion did not change. However, corticopapillary gradient of solutes was significantly increased in CPMD-treated rats. Higher tissue osmolality was due to significantly increased concentration of Na+, and to a lesser degree urea, in the medulla and papilla of CPMD-treated rats. Consequently, the osmotic gradient between urine and papillary tissue of CPMD-treated rats (A = 385±47 mosM) was significantly (P < 0.001) higher compared with controls (A = 150±26 mosM). Minimum urine osmolality after water loading was higher in CPMD-treated DI rats than in controls. Oxidation of ['4C] Based on the findings recounted above, we propose a hypothesis that CPMD administration enhances the antidiuretic effect of VP, primarily by increasing medullary and papillary tonicity due to increased NaCl reabsorption in MAL. There is no evidence that CPMD sensitizes collecting tubules to the action of VP, at least at the cAMP-generation step. Therefore, increased antidiuretic response to VP in the kidneys of CPMDtreated DI rats is due to enhanced osmotic driving force for water reabsorption (lumen-to-interstitium osmotic gradient) in collecting tubules, rather than due to increased VP-dependent water permeability of tubular epithelium.

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Chlorpropamide action on renal concentrating mechanism in rats with hypothalamic diabetes insipidus.

Kusano¹,

Braun-Werness²,

Vick³

et al. 1983

J. Clin. Invest.

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“…Inspite of side effects like hypoglycemia, central nervous system problems and skin reactions, [10][11][12] glibenclamide, a second generation sulfonylurea drug, is being used widely due to its safe administration with other drugs, low production of diuresis, no significant antidiuretic effect, no or low disulfiran like reaction as well as dual route of excretion without effecting glucose tolerance. [13][14][15][16] It is found that complexes of some active drugs are more effective than the ligand themselves. [17][18][19][20][21] It is the reason that transition metal complexes of established drugs are gaining much biological significance.…”

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Synthesis, Characterization and Hypoglycemic Activity of Zn(II), Cd(II) and Hg(II) Complexes with Glibenclamide

Rasheed

Tariq

Munir

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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Inorganic elements play crucial roles in biological and biomedical processes, and it is evident that many organic compounds used in medicine do not have a purely organic mode of action; some are activated or biotransformed by metal ions including metalloenzymes, others have a direct or indirect effect on metal ion metabolism.1,2) Metals like chromium, zinc, vanadium, copper, selenium, etc., have been reported in lowering the blood sugar level (Hypoglycemia). At the molecular and cellular level, zinc is intimately involved in insulin synthesis, secretion and signalling, and thus, the consequent actions of insulin on metabolism.3,4) In addition to antiviral, antibacterial, antifungal and anticancer properties, 5) various clinical and epidemiological studies suggest that reduced Zn status is associated with diabetes.3,4,6,7) Moreover, zinc is known to be essential for the function and/or structure of several enzymes e.g.; dehydrogenases, aldolases, peptidases, phosphatases, an isomerase, a transphosphorylase, aspartate transcarbamylase, pancreatic carboxpeptidase, and tryptophan desmolase. 8) Zinc-dependent metalloenzymes are also found among oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases. 9)Sulfonylureas have received much attention because of their pharmacological activities in the treatment of non-insuline dependent diabetes mellitus (NIDDM) to enhance the sensitivity of tissues to insulin and to stimulate the pancreas to secrete more insulin and comprise the largest group of oral hypoglycemic agents. These are structurally dissimilar, differing primarily with respect to the substituent R at para position of the benzene ring and the group attached to the terminal urea nitrogen RЈ (1). Inspite of side effects like hypoglycemia, central nervous system problems and skin reactions, [10][11][12] glibenclamide, a second generation sulfonylurea drug, is being used widely due to its safe administration with other drugs, low production of diuresis, no significant antidiuretic effect, no or low disulfiran like reaction as well as dual route of excretion without effecting glucose tolerance. [13][14][15][16] It is found that complexes of some active drugs are more effective than the ligand themselves. [17][18][19][20][21] It is the reason that transition metal complexes of established drugs are gaining much biological significance. [22][23][24] The chemistry of sulphonylureas and their metal complexes have created great interest and enthusiasm among the chemists because of their pharmacological importance. Some studies on the coordination chemistry of sulphonylurea drug with Zn 2ϩ , Cd 2ϩ and Hg 2ϩ metals ions have been carried out which is an attempt to examine the mode of action and drug delivery. 25,26) Keeping in view the concept of coordination of suitable metals as central atom, the biologically active compounds often become more effective than desirable drugs. 27) Hence, the objective of this study was to synthesize a metal based drug after long term clinical studies establishing safety (la...

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“…In con trast, three other sulfonylurea preparations, tolazamide, acetohexamide, and glybenclamide. produce different results, i.e., di uresis in water-loaded normal subjects and animals [10][11][12][13][14][15][16], The mechanism of action for the latter is still uncertain. The present 1 Supported by a grant from Pfizer Pharmaceuticals, Inc. study was undertaken to investigate the ef fects of acute low-dose administration of gli pizide, a sulfonylurea with hypoglycemic potential [17], on salt and water handling of water-loaded normal human subjects.…”

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Effects of Glipizide on Water and Electrolyte Handling in Water-Loaded Humans

Preuss¹,

Rodelas²,

Terlinsky³

et al. 1981

Kidney Blood Press Res

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Renal handling of H₂O, Na, and K during H₂O diuresis was studied in the same healthy subjects on two occasions, after the administration of either 5 mg of the sulfonylurea, glipizide, or a placebo. Following glipizide, there was no significant overall change in creatinine clearance and the calculated rate of distal Na + K delivery (C_H2O + C_(Na₊_K)) in 9 individuals. However, the clearance of free water (C_H2O) and the mean fraction of Na + K reabsorbed at the diluting site increased significantly from 8.5 ± (SEM) 0.8 to 9.8 ± (SEM) 0.8 ml/min/100 ml GFR (p < 0.02) and from 55 ± (SEM) 6 to 67 ± (SEM) 7% (p < 0.05), respectively. The mean rate of total Na and K excretion fell following glipizide (p < 0.05). Our results, in conjunction with the results from similar type studies, suggest that ingestion of glipizide and other sulfonylureas that lack antidiuretic properties increase C_H2O, at least in part, by augmenting ion reabsorption at the diluting sites of the nephron.

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Diuretic Action of Three Sulfonylurea Drugs

Cited by 72 publications

References 17 publications

Chlorpropamide action on renal concentrating mechanism in rats with hypothalamic diabetes insipidus.

Chlorpropamide action on renal concentrating mechanism in rats with hypothalamic diabetes insipidus.

Synthesis, Characterization and Hypoglycemic Activity of Zn(II), Cd(II) and Hg(II) Complexes with Glibenclamide

Effects of Glipizide on Water and Electrolyte Handling in Water-Loaded Humans

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