Aminopyrine-N-demethylase I. Directed modification of substrates’ structure as a way of production of inducer of the monooxygenase isoform P-450b

  title={Aminopyrine-N-demethylase I. Directed modification of substrates’ structure as a way of production of inducer of the monooxygenase isoform P-450b},
  author={L. B. Tsyrlov and K. E. Gerasimov},
  journal={European Journal of Drug Metabolism and Pharmacokinetics},
SummaryThe effect of the phenobarbital-type monooxygenase inducers is accomplished via the native molecule. This made it possible to transform the typical substrate of cytochrome P-450b aminopyrine into an inducer of this isozyme by blocking the substrate molecule position undergoing monooxygenation. Substitution of two methyl groups in the aminopyrine -N(CH3)2 position by an isopropyl group gave rise to a clear-cut inducive effect This was registered by spectral, kinetic, radiological and… Expand
Aminopyrine-N-demethylase. II. Characterization of a unique monooxygenase isoform P-450ap
It was, demonstrated that cytochrome P-450ap does not interact with the antibodies to the major phenobarbital induced form, i.e. with cyto chrome P- 450b. Expand
Mitragyna speciosa Korth leaves extracts induced the CYP450 catalyzed aminopyrine-N-demethylase (APND) and UDP-glucuronosyl transferase (UGT) activities in male Sprague-Dawley rat livers
It is shown that possibilities exist for herb-drug interaction with increased clearance of drugs, which are primarily metabolized by CYP450s and UGT1A6 among M. speciosa leaves extract users. Expand
Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitus
For drugs mainly metabolized via hepatic CYP isozymes, the changes in the total area under the plasma concentration–time curve from time zero to time infinity (AUC) of metabolites, AUCmetabolite/AUCparent drug ratios, or the time‐averaged nonrenal and total body clearances of parent drugs as reported in the literature have been compared. Expand


[Characteristics of induced aminopyrine N-demethylase].
: The study of the inducing effect of phenobarbital on the activity of N-demethylase of aminopyrine in the rat liver microsomes revealed the correlation of the rate of enzymic reaction with theExpand
Investigation of the type of induction of microsomal monooxygenases by polycyclic hydrocarbons.
It is concluded that in the mechanism of induction by 3-methylcholanthrene, the activation of synthesis of specific protein is accomplished not by the initial molecule of the inducer, but by products of its primary metabolism in the microsomes. Expand
Effect of chlorinated naphthalenes and terphenyls on the activities of drug metabolizing enzymes in rat liver.
  • M. Ahotupa, A. Aitio
  • Chemistry, Medicine
  • Biochemical and biophysical research communications
  • 1980
Chlorinated naphthalenes with high chlorine content, Halowax 1014 andHalowax 1051 (containing 62 and 70 wt.−% Cl, respectively), were potent inducers of enzymes catalyzing drug hydroxylation or glucuronidation in rat liver, and the activities of epoxide hydratase and glutathione S-transferase were not altered after treatment of animals. Expand
Structure-activity relationships in polycyclic aromatic hydrocarbons: induction of microsomal aryl hydrocarbon hydroxylase and its possible importance in chemical carcinogenesis.
  • R. Franke
  • Chemistry, Medicine
  • Chemico-biological interactions
  • 1973
Abstract The results of quantitative structure-activity analysis show that the potency of polycyclic hydrocarbons as inducers of microsomal arylhydrocarbon hydroxylase (AHH) can be quantitativelyExpand
Possible mechanism of induction of liver microsomal monooxygenases by phenobarbital.
The data presented indicate that the location of the CO-peak of Na2S2O4-reduced hemoprotein is not the criterion of monooxygenase functional specificity; the latter may, possibly, be defined by the relation between the contents of the high-spin and low-spin species of the cytochrome. Expand
Induction of drug metabolizing enzyme system in the liver
  • H. Remmer
  • Biology
  • European Journal of Clinical Pharmacology
  • 2004
Summary1. Accelerated drug metabolism in liver cells was discovered during studies of the cause of barbiturate tolerance and of the way in which polycyclic hydrocarbons protect against the actions ofExpand
Regulation of three forms of cytochrome P-450 and epoxide hydrolase in rat liver microsomes. Effects of age, sex, and induction.
The preparation of monospecific antibody directed against rat liver microsomal cytochrome P-45-a has been used to show that these three forms of cytochromes P-450 are distinct and share no common antigenic determinants. Expand
Induction of microsomal enzyme synthesis by polycyclic aromatic hydrocarbons of different molecular sizes.
Evidence is presented here that there is an optimal molecular size range for the polycyclic aromatic hydrocarbons to induce the synthesis of microsomal enzymes in the rat liver. Expand
Separation of pure polychlorinated biphenyl isomers into two types of inducers on the basis of induction of cytochrome P-450 or P-448.
Isomers which are chlorinated in only one ring, or are chlorination in both rings but not in the para positions, have very little activity as inducers of liver enzymes. Expand
Structure-activity relationships in halogenated biphenyls: unifying hypothesis for structural specificity.
It was concluded that the most stable conformation of all biphenyls with or without ortho-substitutents is non-planar and that neigher planarity nor symmetry is an inherent requirement for receptor binding. Expand