Effect of the novel anxiolytic drug deramciclane on cytochrome P450 2D6 activity as measured by desipramine pharmacokinetics

@article{Laine2003EffectOT,
  title={Effect of the novel anxiolytic drug deramciclane on cytochrome P450 2D6 activity as measured by desipramine pharmacokinetics},
  author={Kari Laine and Steven De Bruyn and Harry Bj{\"o}rklund and Juha Rouru and Jutta H{\"a}nninen and Harry Scheinin and Markku I. Anttila},
  journal={European Journal of Clinical Pharmacology},
  year={2003},
  volume={59},
  pages={893-898}
}
BackgroundIn vitro findings have indicated that the novel anxiolytic drug, deramciclane, is an inhibitor of the cytochrome P450 (CYP) 2D6 enzyme and co-administration of deramciclane and the CYP2D6 probe drug desipramine is possible in clinical practice.ObjectiveTo evaluate the effects of deramciclane on CYP2D6 activity as measured by desipramine pharmacokinetics and pharmacodynamics using paroxetine as a positive control for CYP2D6 inhibition.MethodsFifteen healthy subjects received either 60… 

The effect of mirabegron, a potent and selective β3-adrenoceptor agonist, on the pharmacokinetics of CYP2D6 substrates desipramine and metoprolol

TLDR
In conclusion, mirabegron is a moderate CYP2D6 inhibitor (ratio and 90 % CI <5.0).

Desipramine, substrate for CYP2D6 activity: population pharmacokinetic model and design elements of drug-drug interaction trials.

TLDR
The semi-mechanistic population model developed is suitable to describe the pharmacokinetic behaviour of desipramine for the dose routinely used in drug-drug interaction (DDI) studies and a sample size of 21 subjects in cross-over design is appropriate for assessing CYP2D6 interaction with novel compounds.

ROLE OF CYP 2 E 1 IN DERAMCICLANE METABOLISM

TLDR
The aim of this study was to identify the form(s) of cytochrome P450 responsible for the metabolism of deramciclane, a new anxiolytic drug candidate, and to influence directly the activity of CYP2E1.

ROLE OF CYP2E1 IN DERAMCICLANE METABOLISM

TLDR
The aim of this study was to identify the form(s) of cytochrome P450 responsible for the metabolism of deramciclane, a new anxiolytic drug candidate, and to establish the main routes of biotransformation in hepatic microsomes.

MECHANISM-BASED INACTIVATION OF CYP 2 D 6 BY METHYLENEDIOXYMETHAMPHETAMINE

  • Biology, Chemistry
  • 2004
TLDR
The results indicate that MDMA is a potent mechanism-based inhibitor of CYP2D6, with implications for understanding its in vivo disposition and drug interaction potential.

MECHANISM-BASED INACTIVATION OF CYP2D6 BY METHYLENEDIOXYMETHAMPHETAMINE (MDMA)

TLDR
The results indicate that MDMA is a potent mechanism-based inhibitor of CYP2D6, with implications for understanding its in vivo disposition and drug interaction potential.

Predictions of Cytochrome P450-Mediated Drug-Drug Interactions Using Cryopreserved Human Hepatocytes: Comparison of Plasma and Protein-Free Media Incubation Conditions

TLDR
The HHSHP system proved to be a simple, accurate predictor of DDIs for three major P450s and superior to the protein-free approach, with a general underprediction by the free with HMM Ki, app method, consistent with an underestimation of in vitro inhibition potency in this system.

CYP 2 D 6 CATALYZES 5-HYDROXYLATION OF 1-( 2-PYRIMIDINYL )-PIPERAZINE , AN ACTIVE METABOLITE OF SEVERAL PSYCHOACTIVE DRUGS , IN HUMAN LIVER MICROSOMES

TLDR
Results indicate that polymorphic CYP2D6 is responsible for the conversion of 1-PP to HO-1-PP, a major urinary metabolite resulting from the N-dealkylation of several antidepressant/anxiolytic 5-HT1A agonists including buspirone.

Predictions of CYP-Mediated Drug-Drug Interactions Using Cryopreserved Human Hepatocytes: Comparison of Plasma and Protein-Free Media Incubation Conditions

TLDR
The HHSHP system proved to be a simple, accurate predictor of DDIs for 3 major CYPs and superior to the protein-free approach, which is consistent with an underestimation of in vitro inhibition potency in this system.

CYP2D6 CATALYZES 5-HYDROXYLATION OF 1-(2-PYRIMIDINYL)-PIPERAZINE, AN ACTIVE METABOLITE OF SEVERAL PSYCHOACTIVE DRUGS, IN HUMAN LIVER MICROSOMES

TLDR
Results indicate that polymorphic CYP2D6 is responsible for the conversion of 1-PP to HO-1-PP, the major metabolite in the human circulation and in rat brains following oral administration of buspirone.

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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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