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The Journal of Clinical Investigation Sep 1972Long-term clinical studies have associated tolbutamide therapy with an increased incidence of cardiovascular deaths. The effects of this and other sulfonylurea drugs on...
Long-term clinical studies have associated tolbutamide therapy with an increased incidence of cardiovascular deaths. The effects of this and other sulfonylurea drugs on contractility and rate of isolated rabbit atria, automaticity of isolated dog Purkinje fibers, and adenyl cyclase activity in particulate preparations of rabbit and human hearts were studied. At concentrations that are attained clinically, tolbutamide (10 mg/100 ml) increased contractility of driven rabbit atria to 124+/-5% of control, acetohexamide (3.9 mg/100 ml) to 140+/-5%, chlorpropamide (8.3 mg/100 ml) to 139+/-6%, and tolazamide (3.1 mg/100 ml) to 119+/-6%. These effects were accentuated in the presence of 2.5 x 10(-4) M theophylline and were not blocked by 1 x 10(-5) M propranolol. Adenyl cyclase was activated by each of these drugs at concentrations below those which increase contractility. The drugs also increased the rate and slope of phase 4 depolarization in spontaneously beating Purkinje fibers, but did not alter the spontaneous rate of isolated rabbit atria. Since inotropic and chronotropic stimulation can be deleterious in some clinical settings, these findings may be of significance in interpretation of cardiovascular mortality data.
Topics: Acetohexamide; Adenylyl Cyclases; Animals; Chlorpropamide; Culture Techniques; Cyclic AMP; Dogs; Heart; Heart Atria; Heart Conduction System; Humans; Membrane Potentials; Microelectrodes; Myocardium; Phenformin; Propranolol; Rabbits; Stimulation, Chemical; Sulfonylurea Compounds; Theophylline; Tolazamide; Tolbutamide
PubMed: 4344732
DOI: 10.1172/JCI107056 -
Yakugaku Zasshi : Journal of the... 2019In this study, we attempted to improve the non-aqueous titration method using N,N-dimethylformamide (DMF) in the Japanese Pharmacopoeia seventeenth edition (JP XVII) for...
In this study, we attempted to improve the non-aqueous titration method using N,N-dimethylformamide (DMF) in the Japanese Pharmacopoeia seventeenth edition (JP XVII) for advancement in experimental safety. As an alternative solvent for DMF, we demonstrate titrations using dimethyl sulfoxide (DMSO), which has similar properties as and much higher safety than DMF. Five drugs (i.e., acetohexamide, glibenclamide, sulfamethoxazole, tranilast, and furosemide) listed in JP XVII use DMF as a solvent for titrations with sodium hydroxide standard solution. For these drugs, we examined whether DMF can be replaced with DMSO in quantitative analyses. As a result, a quantification similar to that of the Pharmacopoeia protocol is possible by simply replacing DMF with DMSO or using a mixed solvent of DMSO and water.
Topics: Dimethyl Sulfoxide; Dimethylformamide; Japan; Pharmacopoeias as Topic; Quality Improvement; Safety; Sodium Hydroxide; Solutions; Solvents; Titrimetry; Water
PubMed: 31474635
DOI: 10.1248/yakushi.19-00119 -
Journal of Chromatography. B,... Nov 2010This report examines the use of high-performance affinity chromatography as a screening tool for studying the change in binding by sulfonylurea drugs to the protein...
This report examines the use of high-performance affinity chromatography as a screening tool for studying the change in binding by sulfonylurea drugs to the protein human serum albumin (HSA) during diabetes. The effects of both the non-enzymatic glycation of HSA and the presence of fatty acids on these interactions were considered using a zonal elution format. It was found that there was a significant increase (i.e., 2.7- to 3.6-fold) in the relative retention of several sulfonylurea drugs (i.e., acetohexamide, tolbutamide, glybenclamide and gliclazide) on columns containing normal versus glycated HSA. The addition of various long chain fatty acids to the mobile phase gave the same trend in retention for the tested drugs on both the HSA and glycated HSA columns, generally leading to lower binding. Most of the fatty acids examined produced similar or moderately different relative shifts in retention; however, palmitic acid was found to produce a much larger change in retention on columns containing glycated HSA versus normal HSA under the conditions used in this study.
Topics: Chromatography, Affinity; Diabetes Mellitus; Fatty Acids; Glycosylation; Humans; Hypoglycemic Agents; Kinetics; Protein Binding; Serum Albumin; Sulfonylurea Compounds
PubMed: 20974553
DOI: 10.1016/j.jchromb.2010.09.033 -
Archives of Disease in Childhood Oct 1970Three infants whose diabetic mothers were given chlorpropamide and one infant whose diabetic mother was given acetohexamide up to the time of delivery were studied in...
Three infants whose diabetic mothers were given chlorpropamide and one infant whose diabetic mother was given acetohexamide up to the time of delivery were studied in the neonatal period because each became severely hypoglycaemic. The sulphonylurea drugs given to the mother crossed the placenta, and fetal plasma concentrations were in the therapeutic range for adults with diabetes mellitus. Each baby had severe hyperinsulinaemia resulting in profound hypoglycaemia. These acutely ill infants needed vigorous and prolonged treatment to correct the hypoglycaemia. In two infants exchange transfusion was performed to remove the drug. These sulphonylurea drugs should not be used to control diabetes mellitus in pregnancy.
Topics: Acetohexamide; Chlorpropamide; Exchange Transfusion, Whole Blood; Female; Fetus; Humans; Hypoglycemia; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy in Diabetics
PubMed: 5477685
DOI: 10.1136/adc.45.243.696 -
Effects of puromycin, acetoxycycloheximide and actinomycin D on protein synthesis in goldfish brain.Journal of Neurochemistry Oct 1966
Topics: Acetohexamide; Animals; Brain; Dactinomycin; Fishes; In Vitro Techniques; Injections, Intraperitoneal; Leucine; Nerve Tissue Proteins; Puromycin; Tritium
PubMed: 5927758
DOI: 10.1111/j.1471-4159.1966.tb10284.x -
Brain Research Feb 1977In further studies on axonally transported protein in the goldfish visual system, the turnover of rapidly transported [3H]proline-labeled protein was examined. It was...
In further studies on axonally transported protein in the goldfish visual system, the turnover of rapidly transported [3H]proline-labeled protein was examined. It was found that: (1) a fraction of the rapidly transported protein has a relatively short half-life; (2) [3H]proline released following proteolysis of transported protein is efficiently reutilized for tectal protein synthesis, as inferred from an increased labeling of nuclear protein in the contralateral tectum (COT) relative to that in the ipsilateral tectum (IOT); (3) a small amount of [3H]proline arrives in the COT by axonal flow of the free amino acid; and (4) [3H]leucine and [3H]asparagine are less efficiently reutilized than [3H]proline. These findings may relate to the phenomenon of transneuronal transfer of radioactivity which has been observed with [3H]proline as precursor. The extensive reutilization of [3H]proline may account for part or all of the labeling at secondary synaptic sites. The results suggest that asparagine may be highly suitable for radioautographic identification of primary neuronal fields.
Topics: Acetohexamide; Animals; Asparagine; Axonal Transport; Axons; Cycloheximide; Goldfish; Hydroxyproline; Leucine; Nerve Tissue Proteins; Optic Nerve; Proline; Superior Colliculi
PubMed: 65202
DOI: 10.1016/0006-8993(77)90292-x -
British Medical Journal Sep 1972
Topics: Acetohexamide; Body Weight; Chlorpropamide; Diabetes Mellitus; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Tolazamide; Tolbutamide
PubMed: 4631184
DOI: 10.1136/bmj.3.5828.692 -
The Tohoku Journal of Experimental... Aug 1974
Topics: Acetohexamide; Blood Glucose; Cholesterol; Clofibrate; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Humans; Lipoprotein Lipase; Male; Middle Aged; Phospholipids; Triglycerides
PubMed: 4446025
DOI: 10.1620/tjem.113.343 -
Canadian Medical Association Journal Nov 1971
Topics: Acetohexamide; Chlorpropamide; Diabetes Mellitus; Diet, Diabetic; Female; Health Education; Humans; Insulin; Male; Patient Care Team; Personality; Phenformin; Pregnancy; Pregnancy in Diabetics; Tolbutamide
PubMed: 5150198
DOI: No ID Found