tolterodine-tartrate and quinone-methide

tolterodine-tartrate has been researched along with quinone-methide* in 2 studies

Other Studies

2 other study(ies) available for tolterodine-tartrate and quinone-methide

Article	Year
In Vitro and In Vivo Metabolic Activation of Tolterodine Mediated by CYP3A. Chemical research in toxicology, 2023, 03-20, Volume: 36, Issue:3 Tolterodine (TOL) is an antimuscarinic drug used for the treatment of patients with overactive bladder presenting urinary frequency, urgency, and urge incontinence. During the clinical use of TOL, adverse events such as liver injury took place. The present study aimed at the investigation of the metabolic activation of TOL possibly associated with its hepatotoxicity. One GSH conjugate, two NAC conjugates, and two cysteine conjugates were found in both mouse and human liver microsomal incubations supplemented with TOL, GSH/NAC/cysteine, and NADPH. The detected conjugates suggest the production of a quinone methide intermediate. The same GSH conjugate was also observed in mouse primary hepatocytes and in the bile of rats receiving TOL. One of the urinary NAC conjugates was observed in rats administered TOL. One of the cysteine conjugates was found in a digestion mixture containing hepatic proteins from animals administered TOL. The observed protein modification was dose-dependent. CYP3A primarily catalyzes the metabolic activation of TOL. Ketoconazole (KTC) pretreatment reduced the generation of the GSH conjugate in mouse liver and cultured primary hepatocytes after TOL treatment. In addition, KTC reduced the susceptibility of primary hepatocytes to TOL cytotoxicity. The quinone methide metabolite may be involved in TOL-induced hepatotoxicity and cytotoxicity. Topics: Activation, Metabolic; Animals; Chemical and Drug Induced Liver Injury; Cysteine; Cytochrome P-450 CYP3A; Glutathione; Humans; Ketoconazole; Mice; Microsomes, Liver; Rats; Tolterodine Tartrate	2023
Enantioselective [4 + 2] cycloadditions of o-quinone methides: total synthesis of (+)-mimosifoliol and formal synthesis of (+)-tolterodine. The Journal of organic chemistry, 2004, Dec-24, Volume: 69, Issue:26 The first example of an enantioselective cycloaddition of an o-quinone methide (o-QM) with a chiral enol ether is described along with the total synthesis of (+)-mimosifoliol and the formal synthesis of (+)-tolterodine. These syntheses exemplify a three-component, one-pot benzopyran approach for the construction of chiral benzylic junctions. Cycloadditions of various enol ethers and o-QMs are examined, and diastereoselectivities >95% are obtained with trans-2-phenyl-1-cyclohexanol and 2,2-diphenylcyclopentanol vinyl ethers. Topics: Acrylates; Benzhydryl Compounds; Cresols; Crystallography, X-Ray; Guaiacol; Indolequinones; Models, Molecular; Phenylpropanolamine; Spectrum Analysis; Stereoisomerism; Tolterodine Tartrate	2004

Article

Year

In Vitro and In Vivo Metabolic Activation of Tolterodine Mediated by CYP3A.

Chemical research in toxicology, 2023, 03-20, Volume: 36, Issue:3

Tolterodine (TOL) is an antimuscarinic drug used for the treatment of patients with overactive bladder presenting urinary frequency, urgency, and urge incontinence. During the clinical use of TOL, adverse events such as liver injury took place. The present study aimed at the investigation of the metabolic activation of TOL possibly associated with its hepatotoxicity. One GSH conjugate, two NAC conjugates, and two cysteine conjugates were found in both mouse and human liver microsomal incubations supplemented with TOL, GSH/NAC/cysteine, and NADPH. The detected conjugates suggest the production of a quinone methide intermediate. The same GSH conjugate was also observed in mouse primary hepatocytes and in the bile of rats receiving TOL. One of the urinary NAC conjugates was observed in rats administered TOL. One of the cysteine conjugates was found in a digestion mixture containing hepatic proteins from animals administered TOL. The observed protein modification was dose-dependent. CYP3A primarily catalyzes the metabolic activation of TOL. Ketoconazole (KTC) pretreatment reduced the generation of the GSH conjugate in mouse liver and cultured primary hepatocytes after TOL treatment. In addition, KTC reduced the susceptibility of primary hepatocytes to TOL cytotoxicity. The quinone methide metabolite may be involved in TOL-induced hepatotoxicity and cytotoxicity.

Topics: Activation, Metabolic; Animals; Chemical and Drug Induced Liver Injury; Cysteine; Cytochrome P-450 CYP3A; Glutathione; Humans; Ketoconazole; Mice; Microsomes, Liver; Rats; Tolterodine Tartrate

2023

Enantioselective [4 + 2] cycloadditions of o-quinone methides: total synthesis of (+)-mimosifoliol and formal synthesis of (+)-tolterodine.

The Journal of organic chemistry, 2004, Dec-24, Volume: 69, Issue:26

The first example of an enantioselective cycloaddition of an o-quinone methide (o-QM) with a chiral enol ether is described along with the total synthesis of (+)-mimosifoliol and the formal synthesis of (+)-tolterodine. These syntheses exemplify a three-component, one-pot benzopyran approach for the construction of chiral benzylic junctions. Cycloadditions of various enol ethers and o-QMs are examined, and diastereoselectivities >95% are obtained with trans-2-phenyl-1-cyclohexanol and 2,2-diphenylcyclopentanol vinyl ethers.

Topics: Acrylates; Benzhydryl Compounds; Cresols; Crystallography, X-Ray; Guaiacol; Indolequinones; Models, Molecular; Phenylpropanolamine; Spectrum Analysis; Stereoisomerism; Tolterodine Tartrate

2004