Delving into the Latest Updates on Tolbutamide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1-Butyl-3-(p-methylphenylsulfonyl)urea, 1-Butyl-3-(p-tolylsulfonyl)urea, 1-Butyl-3-tosylurea

+ [14]

Target

Kir6.2 x SUR1

Mechanism

Kir6.2 stimulants(potassium inwardly rectifying channel subfamily J member 11 stimulants), SUR1 inhibitors(Sulfonylurea receptor 1 inhibitors)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus, Type 2

Inactive Indication-

Originator Organization

Pharmacia & Upjohn, Inc.

Active Organization

Changzhou Pharmaceutical Factory Co., Ltd.

Inactive Organization

Pharmacia & Upjohn, Inc.

Pfizer Inc.

Drug Highest PhaseApproved

First Approval Date

US (31 May 1957),

Diabetes Mellitus, Type 2

Regulation-

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Structure

Molecular FormulaC12H18N2O3S

InChIKeyJLRGJRBPOGGCBT-UHFFFAOYSA-N

CAS Registry64-77-7

A rapid and simple method to measure oral hypoglycemic agents is essential in the evaluation of a patient with spontaneous hypoglycemia. As a result, a robust high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the qualitative detection of first-generation sulfonylureas (e.g., chlorpropamide, tolazamide, and tolbutamide), second-generation sulfonylureas (e.g., glimepiride, glipizide, and glyburide), meglitinides (e.g., repaglinide, nateglinide), and thiazolidinediones (e.g., rosiglitazone and pioglitazone). HPLC involved a C8 column and MS/MS was used in electrospray ionization (ESI) positive mode. Identification of all compounds was made using various multiple-reaction monitoring (MRMs). Isotopic labeled chlorpropamide-d4, glimepiride-d5, glyburide-d11, nateglinide-d5, repaglinide-ethyl-d5, rosiglitazone-d3, and zomepirac were used as the internal standards. The cutoffs for each drug were as follows: chlorpropamide 100 ng/mL, tolazamide 50 ng/mL, tolbutamide 20 ng/mL, glimepiride 20 ng/mL, glipizide 5 ng/mL, glyburide 5 ng/mL, repaglinide 5 ng/mL, rosiglitazone 20 ng/mL, pioglitazone 20 ng/mL, and nateglinide 5 ng/mL.

23 Oct 2023·International journal of molecular sciences

Short-Term Inhibition of Translation by Cycloheximide Concurrently Affects Mitochondrial Function and Insulin Secretion in Islets from Female Mice.

Article

Author: Panten, Uwe ; Morsi, Mai ; Rustenbeck, Ingo ; Schulze, Torben ; Alshafei, Mohammed

Since glucose stimulates protein biosynthesis in beta cells concomitantly with the stimulation of insulin release, the possible interaction of both processes was explored. The protein biosynthesis was inhibited by 10 μM cycloheximide (CHX) 60 min prior to the stimulation of perifused, freshly isolated or 22 h-cultured NMRI mouse islets. CHX reduced the insulinotropic effect of 25 mM glucose or 500 μM tolbutamide in fresh but not in cultured islets. In cultured islets the second phase of glucose stimulation was even enhanced. In fresh and in cultured islets CHX strongly reduced the content of proinsulin, but not of insulin, and moderately diminished the [Ca²⁺]_i increase during stimulation. The oxygen consumption rate (OCR) of fresh islets was about 50% higher than that of cultured islets at basal glucose and was significantly increased by glucose but not tolbutamide. In fresh, but not in cultured, islets CHX diminished the glucose-induced OCR increase and changes in the NAD(P)H- and FAD-autofluorescence. It is concluded that short-term CHX exposure interferes with the signal function of the mitochondria, which have different working conditions in fresh and in cultured islets. The interference may not be an off-target effect but may result from the inhibited cytosolic synthesis of mitochondrial proteins.

20 Oct 2023·Molecules (Basel, Switzerland)

Inhibitory Mechanisms of Lekethromycin in Dog Liver Cytochrome P450 Enzymes Based on UPLC-MS/MS Cocktail Method.

Article

Author: Sun, Pan ; Zhang, Suxia ; Cao, Xingyuan ; Qiu, Jicheng ; Cao, Yuying ; Kong, Jingyuan

Lekethromycin (LKMS) is a synthetic macrolide compound derivative intended for use as a veterinary medicine. Since there have been no in vitro studies evaluating its potential for drug-drug interactions related to cytochrome P450 (CYP450) enzymes, the effect of the inhibitory mechanisms of LKMS on CYP450 enzymes is still unclear. Thus, this study aimed to evaluate the inhibitory effects of LKMS on dog CYP450 enzymes. A cocktail approach using ultra-performance liquid chromatography-tandem mass spectrometry was conducted to investigate the inhibitory effect of LKMS on canine CYP450 enzymes. Typical probe substrates of phenacetin, coumarin, bupropion, tolbutamide, dextromethorphan, chlorzoxazone, and testosterone were used for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4, respectively. This study showed that LKMS might not be a time-dependent inhibitor. LKMS inhibited CYP2A6, CYP2B6, and CYP2D6 via mixed inhibition. LKMS exhibited mixed-type inhibition against the activity of CYP2A6 with an inhibition constant (K_i) value of 135.6 μΜ. LKMS inhibited CYP2B6 in a mixed way, with K_i values of 59.44 μM. A phenotyping study based on an inhibition assay indicated that CYP2D6 contributes to the biotransformation of LKMS. A mixed inhibition of CYP2D6 with K_i values of 64.87 μM was also observed. Given that this study was performed in vitro, further in vivo studies should be conducted to identify the interaction between LKMS and canine CYP450 enzymes to provide data support for the clinical application of LKMS and the avoidance of adverse interactions between other drugs.

1

News (Medical) associated with Tolbutamide

19 Jul 2022

·healthtechinsider.com

New CGM Device for Type 2 Diabetes

MySugarWatch has pushed the pedal on an awareness campaign for its continuous non-invasive glucose monitor called sugarBEAT. MySugarWatch is the UK licensee of Nemaura Medical, a company specializing in developing wearable diagnostic devices. The company aims to cater to the awareness needs of the people with pre-diabetes and diabetes. The campaign, featured in the DailyMail, is set to reach about 1.2 million people. MySugarWatch aims to eliminate skin-pricks test strips historically used by patients to monitor blood sugar level for Type-2 diabetes patients. Studies show that 3.6 million in the UK suffer from Type-2 Diabetes while a further 12.3 million people are at risk of developing the disorder. MySugarWatch adds to the list of continuous glucose monitoring devices. It monitors your blood sugar level every 5 minutes, providing consistent data. The data is then stored in a dedicated app, which maps the 168 glucose level readings taken during the day. This allows you to identify trends and monitor Time-in-Range right from your phone. The device does require calibration with a finger stick; a reading each morning before eating is recommended. Continuous Glucose Monitoring (CGM) was difficult to achieve so far due to difficulties in procedure including regular needle insertion. CGMs like MySugarWatch that measure interstitial fluid glucose levels do not require a needle prick and easily allows patients to make lifestyle changes based on trends in their blood sugar level. These strategic changes will greatly help patients and healthcare professionals to manage, prevent and even reverse Type-2 pre-diabetes. MySugarWatch, unfortunately, is not for Type-1 diabetes patients, or patients who receive injectable insulin or who are taking sulfonylurea medications (Glibenclamide, Gliclazide, Glimepiride, Glipizide, Tolbutamide). As a result, it’s not completely useful as an “artificial pancreas” component. The product does have CE Mark clearance, but not FDA clearance yet.

100 Deals associated with Tolbutamide

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