Corpus ID: 25233062

Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver.

@article{Lemoine1993MajorPO,
  title={Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver.},
  author={A. Lemoine and J. Gautier and D. Azoulay and L. Kiffel and C. Belloc and F. Guengerich and P. Maurel and P. Beaune and J. Leroux},
  journal={Molecular pharmacology},
  year={1993},
  volume={43 5},
  pages={
          827-32
        }
}
The metabolism of imipramine by human liver microsomes was examined using a combination of five strategies. Human hepatic microsomes produced N-desmethylimipramine (84%), 2-hydroxyimipramine (10%), and 10-hydroxyimipramine (6%). Preincubation of human hepatocytes in culture with beta-naphthoflavone and macrolides exclusively induced the formation of desmethylimpramine (552%, p < 0.05, and 234%, p < 0.003, respectively). Correlations were obtained between rates of imipramine demethylation and… Expand
Characterization of the human hepatic cytochromes P450 involved in the in vitro oxidation of clozapine.
TLDR
The data indicate that while both CYP isoforms readily catalyze both metabolic routes in vitro, CYP1A2 and CYP3A4 are more important in N-demethylation and N-oxidation, respectively. Expand
In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes.
TLDR
The studies demonstrate that only CYP3A4 is actively involved in the formation of 3-OH-Q, and the (3S)-3-hydroxylation of quinidine is a specific probe for CYP2C9 and 2E1 activity in human liver microsome preparations. Expand
In vitro metabolism of imipramine by brain microsomes: effects of inhibitors and exogenous cytochrome P450 reductase
TLDR
Results from studies on the incorporation of cytochrome P450 reductase into the brain microsomal system reveal a reductases concentration-dependent increase in imipramine metabolism and suggest that the reduct enzyme level in brain is an important factor for the study of catalytic activities in brain microSomal systems. Expand
Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs.
TLDR
The human liver microsomal study using the near-therapeutic IMI concentration (2 microM) suggests that CYP2C19 and 1A2 are involved in the N-demethylation and the 2-hydroxylation is mediated exclusively by CyP2D6 and partially by CYP1A2 and 2D6 play a major role in IMI N-genetication and 2-Hydroxylations in the PM livers. Expand
Phenacetin O-deethylation by human liver microsomes in vitro: inhibition by chemical probes, SSRI antidepressants, nefazodone and venlafaxine
TLDR
Biotransformation of phenacetin via O-deethylation to acetaminophen, an index reaction reflecting activity of Cytochrome P450-1A2, was studied in microsomal preparations from a series of human livers, consistent with a double Michaelis-Menten system. Expand
CYTOCHROME P 4502 C 9 IS THE PRINCIPAL CATALYST OF RACEMIC ACENOCOUMAROL HYDROXYLATION REACTIONS IN HUMAN LIVER MICROSOMES
The oral anticoagulant acenocoumarol is given as a racemic mixture. The (S)-enantiomer is rapidly cleared and is the reason why only (R)-acenocoumarol contributes to the pharmacological effect. TheExpand
Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes.
  • O. Olesen, K. Linnet
  • Chemistry, Medicine
  • Drug metabolism and disposition: the biological fate of chemicals
  • 1997
The metabolism of nortriptyline was studied in vitro using cDNA-expressed human cytochrome P450 isozymes 1A2, 3A4, 2C19, and 2D6, CYP2D6 was the sole isozyme mediating hydroxylation of nortriptyline,Expand
Involvement of Human CYP 1 A Isoenzymes in the Metabolism and Drug Interactions of Riluzole In Vitro 1
Cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) isoenzymes involved in riluzole oxidation and glucuronidation were characterized in (1) kinetic studies with human hepaticExpand
Main contribution of the cytochrome P450 isoenzyme 1A2 (CYP1A2) to N-demethylation and 5-sulfoxidation of the phenothiazine neuroleptic chlorpromazine in human liver--A comparison with other phenothiazines.
TLDR
The obtained results indicate that the catalysis of chlorpromazine N-demethylation and 5-sulfoxidation in humans exhibits a stricter CYP1A2 preference compared to the previously tested phenothiazines (promazine, perazine, and thioridazine). Expand
Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions in human liver microsomes.
TLDR
It is demonstrated that (S)-acenocoumarol is hydroxylated by a single enzyme, namely CYP2C9, which is also the main enzyme in the 7-hydroxylation of (R)-acenticoagulant therapy. Expand
...
1
2
3
4
5
...