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At least 469 records · Page 26Linked to original sources
PubMed1978

[Hormone and metabolic profile in diabetic hyperosomolar coma. Plasma insulin response to intravenous tolbutamide (author's transl)].

Fifteen patients with non-ketotic hyperosmolar diabetic coma were investigated and compared with ketoacidotic patients. Basal plasma insulin levels were low in all patients (14.8 +/- 1.0 micronU/ml in hyperosmolar coma, 11.0 +/- 1.3 in keto-acidosis), but insulin level increased after intravenous tolbutamide (between 30 and 105 micronU/ml) in eight hyperosmolar comas. Insulin showed no increase in seven hyperosmolar comas and in none of the ketoacidotic patients. In hyperosmolar coma plasma free fatty acids (1710 +/- 197 micronEq/1), triglycerides (3,4 +/- 0,4 g/1) and cortisol levels (49,7 +/- 9,0 microgram/100 ml) were increased, must as in keto-acidosis. Growth hormone (1,7 +/- 0,1 ng/ml) was normal, unlike the case in keto-acidosis. Plasma lactate concentrations were elevated and account for the frequent mild acidosis found in hyperosmolar coma. In spite of the low peripheral "insulin/glycemia ratio", the positive response to tolbutamide in half of the hyperosmolar cases suggests a less complete pancreatic deficiency than in keto-acidosis. The plasma high free fatty acid and triglyceride levels suggest that the lack of ketosis is not due to inhibition of lipolysis but could be a consequence of inhibition of hepatic ketogenesis.

Adult↗
PubMed1986

Tolbutamide kinetics in cigarette smokers in the Indian population.

A single oral dose of 500 mg tolbutamide was administered to 9 chronic cigarette smokers and 8 healthy matched control volunteers. Plasma tolbutamide half-life (t1/2 B) was shortened in cigarette smokers as compared to the nonsmokers, but the difference was not statistically significant (p greater than 0.05). However, the area under the plasma concentration (AUC O----x) and peak concentration (Cmax) were reduced significantly in smokers. Concern over enhanced metabolism of several drugs is probably warranted in cigarette smokers.

Adult↗
PubMed1985

Tolbutamide kinetics in a normal Indian population.

A single oral dose of 500 mg of tolbutamide was administered to 13 healthy volunteers. Plasma tolbutamide half-life was compared between male and female volunteers. The half-life in female subjects was longer as compared to male subjects, but the difference was not statistically significant (p greater than 0.05).

Adult↗
PubMed1983

[1) Temporal structure of endocrine secretion: circannual changes in insulin responsiveness to tolbutamide in man].

In our previous observations we could detect the existence of circadian rhythms of either tolbutamide-induced insulin release with the acrophase early in the morning (at 04.20) or an insulin-induced hypoglycemia with the acrophase at 10.30 a.m. Aim of our work was to extend the observation to circannual rhythms of the same parameters. Four healthy young volunteers were submitted to the study in the early months of the year and observed in a 24 hrs-period, every other month, in the course of one year. 250 mg tolbutamide were injected i.v. in each day of the experiment every four hours with starting points at a random sequence. The data were analyzed by microscopic analysis: Halberg's Cosinor method. The highest insulin release occurred in winter (Acrophase: Jan. 19 with 95% confidence limits: Oct. 31 - April 1).

Adult↗
PubMed1980

[Effect of adenosine triphosphate (ATP) on the secretion of insulin induced by tolbutamide in the absence of glucose].

Our experiments were carried out on the isolated perfused rat pancreas. The effect of ATP on insulin secretion induced by tolbutamide (a hypoglycemic sulfonylurea) was studied in the absence of glucose. The addition of ATP (0.165 mmol/l) to the perfusion medium did not significantly modify the first phase induced by tolbutamide (0.4 mmol/l) but potentiated the second phase.

Adenosine Triphosphate↗
PubMed1983

[Effect of tolbutamide on the electrical activity of bursting neurons in Helix pomatia].

The effect of tolbutamide, an inhibitor of proteinkinase reaction, on electrical activity of the RPal bursting neuron was studied in Helix pomatia. It is shown that 5 mM tolbutamide produced a complete and reversible block of pacemaker activity of the neuron. It is concluded that cell proteinkinase is involved in the genesis of neuronal bursting activity.

Action Potentials↗
PubMed1995

Synthesis and in vivo hypoglycemic screening studies on some life essential metal complexes of oral antidiabetic [N-(p-tolylsulphonyl)-N'-n butyl-urea] (tolbutamide).

Present communication deals with the synthesis of complexes of [N-(p-tolylsulphonyl)-N'-n butyl-urea], with certain transition metals viz. Cu(II), Zn(II), Fe(II) and Cd(II). Structures of all the complexes have been established on the basis of their consistent elemental and spectral analysis. Also, it reports their in vivo hypoglycemic screening on albino rats. Out of all the complexes studied, Zn-Tolbutamide complex could be recommended as more potent hypoglycemic agent in lieu of tolbutamide alone.

Administration, Oral↗
PubMed1995

Regulation of a potassium conductance in rat midbrain dopamine neurons by intracellular adenosine triphosphate (ATP) and the sulfonylureas tolbutamide and glibenclamide.

The presence of adenosine triphosphate-regulated potassium channels (K-ATPs) in midbrain dopamine neurons is currently in dispute. This was investigated using whole-cell patch-clamp recordings from dopamine neurons in slices of midbrain from 9-12-d-old rats. Intracellular dialysis with Mg2+ ATP-free solutions resulted in a membrane hyperpolarization (14 +/- 6 mV), or outward current (102 +/- 27 pA) in voltage clamp, which developed over 14 +/- 1.6 min. These hyperpolarizations and outward currents were reversed by the K-ATP-blocking sulfonylureas tolbutamide (100 microM) and glibenclamide (3 microM). This sulfonylurea-sensitive outward current was associated with an increase in a nonrectifying (between -50 and -130 mV) conductance of approximately 2 nS, with a reversal potential of -100 mV (in 2.5 mM extracellular potassium), consistent with a potassium conductance increase. When the dialyzate contained Mg2+ATP (2 mM), no slowly developing hyperpolarization or outward current occurred, and tolbutamide (200 microM) and glibenclamide (10 microM) did not affect membrane potential or current. Additionally, the "potassium channel activators" (KCAs) lemakalim (200 microM) and pinacidil (50 microM) were also without effect on the membrane potential or holding current in these cells. The hyperpolarizations and outward currents caused by baclofen and quinpirole, agonists at GABAB and D2 receptors, respectively, were neither blocked by sulfonylureas nor occluded by the current resulting from depletion of intracellular ATP. Thus, these K-ATPs appear independent of the potassium channels coupled to GABAB and D2 receptors in these cells. This ATP-regulated potassium conductance may constitute a protective mechanism during anoxia or hypoglycemia, by restricting membrane depolarization of dopamine neurons when intracellular ATP levels fall.

Adenosine Triphosphate↗
PubMedDate not supplied

[Differences found in serum serotonin between a group of normal and subjects of obese patients following intravenous tolbutamide administration].

We have studied the effect of the i.v. administration of 1 g tolbutamide upon glycemia, insulinemia and serotoninemia in normal subjects and obese patients. We have seen an elevation of the last two variables in direct relationship with the previous blood sugar levels. The baseline serotonin level in obese people is higher than in normals, but the tolbutamide induced elevation is of a lesser magnitude. We believe this fact is due to the competitive action of insulin, as our obese patients have shown to have a "hyperinsulinism" with "disinsulinism".

Female↗
PubMed1976

[A contribution to the identification of the oral antidiabetic agent tolbutamide. 1st communication].

An identification reaction for tolbutamide given in several pharmacopoeias involves the reaction of n-butylamine, formed by acid hydrolysis of tolbutamide, with diazotised p-nitroaniline to yield a characteristic red colour of unknown structure(s). It is demonstrated that, by using TLC methods, this red colour can be separated into 8 red or yellow coloured components. The structures of these isolated compounds were determined by spectroscopical methods and, in six cases, confirmed by unequivocal synthesis. These coloured components include one pentazdiene, five triazenes and two nitro compounds.

Aniline Compounds↗
PubMed1986

[Extracellular ATP potentiates the secretion of insulin induced by tolbutamide].

Our experiments were carried out on the isolated perfused rat pancreas. The effect of extracellular ATP (8 microM) on insulin secretion induced by tolbutamide (0.04 mM) was studied in the presence of substimulating glucose concentration 4.2 mM (0.75 g/l). ATP (8 microM), ineffective per se at this concentration, highly potentiated the insulin secretion induced by tolbutamide (0.04 mM).

Adenosine Triphosphate↗
PubMed1996

Putative active site template model for cytochrome P4502C9 (tolbutamide hydroxylase).

Binding of substrates to the active site of cytochrome P450 enzymes largely relies on hydrophobic interactions. However, other binding interactions can take place giving the enzyme high regioselectivity and even stereoselectivity. For instance, within the major human cytochrome P450s involved in drug metabolism, cytochrome P4502D6 (CYP2D6) relies on an ion-pair interaction as a major binding factor. There are now a number of substrates reported that have routes of metabolism ascribed specifically to cytochrome P4502C9 (CYP2C9), the isoform mainly responsible for tolbutamide hydroxylation. Although chemically diverse, these substrates have the capability to be hydrogen bond donors (or acceptors). The substrate specificity has been rationalized in terms of a hydrogen bond donor/acceptor model and, by use of molecular modeling, an active site template model for CYP2C9 has been generated. The substrates modeled were phenytoin, warfarin, ibuprofen, naproxen, diclofenac, delta 1-tetrahydrocannabinol, 58C80, and tolbutamide. In addition to the substrates, the potent, selective inhibitor sulfaphenazole was also included in the modeling. An initial hydrogen bond donor site (N2) was identified on phenytoin, the most rigid of the substrates. Corresponding hydrogen bond donation sites were then identified on all of the molecules studied. Using molecular modeling, the site of metabolism and the hydrogen bond donation sites of the molecules were then overlaid on phenytoin to produce the putative active site model. The resultant model is described by a, the distance between the site of metabolism (Y), and the hydrogen bond donor heteroatom (X) and C, the angle between this and the hydrogen bond. The mean dimensions (+/- SD) for the nine substrates and one inhibitor (a = 6.7 +/- 1.0 A, C = 133 +/- 21 degrees) illustrate the degree of overlap achieved.

Aryl Hydrocarbon Hydroxylases↗
PubMed1965

A COMPARATIVE STUDY OF SOME BRANDS OF TOLBUTAMIDE AVAILABLE IN CANADA. II. PHARMACEUTICAL ASPECTS.

Pharmaceutical analyses were carried out on 26 lots of tolbutamide from 21 manufacturers. All lots were found to be satisfactory with respect to identity and strength. Disintegration time of 24 lots ranged from one to 35 minutes, with 72 and 83 minutes for the other two. The time to 90% dissolution in intestinal solution (pH 7.5) ranged from five to 69 minutes in all except two lots for which the times were 99 and over 120 minutes. While the clinical significance of these findings cannot be ascertained in the absence of data from controlled studies, the evidence does not suggest that most of the non-proprietary products available in Canada would not be satisfactory for the purpose intended.

Androsterone↗
PubMed1978

Influence of corticosteroid on hexobarbital and tolbutamide disposition.

The influence of 10 days' prednisone treatment on the disposition of hexobarbital and tolbutamide was studied in 7 healthy male volunteers. No significant changes in the pharmacokinetic parameters of the two drugs became apparent, which indicates that prednisone pretreatment does not affect their metabolic activities.

Adult↗
PubMed1976

Tolbutamide treatment of pregnant mice: repeated administration reduces fetal lethality.

Pretreatment of pregnant BALB/c mice with several low doses of tolbutamide protected against the fetolethal effects of a high dose. Pregnant mice were given single ip injections of 400 mg/kg in saline on day 13; 100 mg/kg/day on days 10, 11, 12, and 13; or 100 mg/kg/day on days 10, 11, and 12 and 400 mg/kg on day 13. On day 16 the single-treatment group had a significantly higher resorption rate than any other group. Fetolethality was not related to hypoglycemia. The protective effect of pretreatment may have been due to induction of maternal microsomal enzymes.

Abnormalities, Drug-Induced↗
PubMed1993

Tolbutamide- and diazoxide-sensitive K+ channel in neurons of substantia nigra pars reticulata.

Single-channel K+ currents were recorded in cell-attached patches from slices of rat substantia nigra. On the somata of neurons in the caudal half of the substantia nigra pars reticulata a K+ selective channel with a unitary conductance of 71 pS (154 mmol/l K+ in pipette filling solution) was identified. The channel was activated both by application of diazoxide (300 mumol/l) and by energy-depleting conditions (200 mumol/l cyanide) and was reversibly blocked by tolbutamide (0.1-1 mmol/l). It is concluded that neurons in the substantia nigra pars reticulata of the rat contain a typical ATP-sensitive K+ channel the activity of which can be modulated by diazoxide and sulfonylureas.

Adenosine Triphosphate↗