Glossary entry (derived from question below)
Spanish term or phrase:
potente inhibidor del mecanismo de inhibición de CYP2D6
English translation:
potent mechanism-based inhibitor of CYP2D6
Added to glossary by
Adam Burman
Nov 5, 2006 09:57
18 yrs ago
7 viewers *
Spanish term
United Kingdom
potente inhibidor del mecanismo de inhibición de CYP2D6
Spanish to English
Medical
Medical: Pharmaceuticals
Investigator's brochure
I think the original is a bit suspect. If not can anyone explain what is being said here?
La paroxetina, el control positivo, resultó un potente inhibidor del mecanismo de inhibición de CYP2D6.
El DSV-233 no mostró el mecanismo de inhibición de la actividad de CYP2D6 en los microsomas hepáticos humanos.
Literal: Paroxetine, the positive control, was a potent inhibitor of the CYP2D6 mechanism of inhibition.
My interpretation: Paroxetine, the positive control, was a potent mechanism-based inhibitor of CYP2D6.
La paroxetina, el control positivo, resultó un potente inhibidor del mecanismo de inhibición de CYP2D6.
El DSV-233 no mostró el mecanismo de inhibición de la actividad de CYP2D6 en los microsomas hepáticos humanos.
Literal: Paroxetine, the positive control, was a potent inhibitor of the CYP2D6 mechanism of inhibition.
My interpretation: Paroxetine, the positive control, was a potent mechanism-based inhibitor of CYP2D6.
Proposed translations
(English)
Proposed translations
+1
4 hrs
Selected
potent [mechanism-based] inhibitor of CYP2D6/ [through mechanism-based inhibition]
I think the "mechanism-based" bit is important and should be included..
See:
of Clinical Psychopharmacology - Fulltext: Volume 25(3 ...
Other antidepressants, such as paroxetine, have been shown to inhibit CYP2D6 through mechanism-based (irreversible) inhibition, but bupropion has not been ...
psychopharmacology.com/pt/re/jclnpsychopharm/fulltext.00004714-200506000-00005.htm;jsessionid=GGmL2YQQy9d... - Similar pages
[PDF] CYP2D6 Inhibition by Fluoxetine, Paroxetine,
Thieme-connect - Abstract
... stronger than the known mechanism-based inhibitor, paroxetine (a positive control). Thus, 15 and 17 are potent mechanism-based inhibitors of CYP2D6. ...
www.thieme-connect.com/ejournals/abstract/plantamedica/doi/... - Similar pages
Mechanism-Based Inhibition of Human Liver Microsomal Cytochrome P450 2D6 (CYP2D6) by Alkamides of Piper nigrum
Subehan1, Tepy Usia1, Shigetoshi Kadota1, Yasuhiro Tezuka1,2
1 Institute of Natural Medicine, University of Toyama, Toyama, Japan
2 21st Century COE Program, University of Toyama, Toyama, Japan
Abstract
Nineteen alkamides isolated from Piper nigrum L. were tested for their mechanism-based inhibition on human liver microsomal dextromethorphan O-demethylation activity, a prototype marker for cytochrome P450 2D6 (CYP2D6). All compounds increased their inhibitory activity with increasing preincubation time. Among them, 15 and 17 showed more than 50 % decrease of the CYP2D6 residual activity after 20 min preincubation. Further investigations on 15 and 17 showed that the characteristic time- and concentration-dependent inhibition, which required a catalytic step with NADPH, was not protected by nucleophiles, and was decreased by the presence of a competitive inhibitor. The kinetic parameters for inactivation (kinact and KI) were 0.028 min-1 and 0.23 μM for 15 and 0.064 min-1 and 0.71 μM for 17, respectively, which were stronger than the known mechanism-based inhibitor, paroxetine (a positive control). Thus, 15 and 17 are potent mechanism-based inhibitors of CYP2D6.
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Note added at 4 hrs (2006-11-05 14:08:20 GMT)
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Please note: As far as I understand, the study points out that Paroxetine IS a potent mechanism-based inhibitor, as opposed to DSV-233.
See:
of Clinical Psychopharmacology - Fulltext: Volume 25(3 ...
Other antidepressants, such as paroxetine, have been shown to inhibit CYP2D6 through mechanism-based (irreversible) inhibition, but bupropion has not been ...
psychopharmacology.com/pt/re/jclnpsychopharm/fulltext.00004714-200506000-00005.htm;jsessionid=GGmL2YQQy9d... - Similar pages
[PDF] CYP2D6 Inhibition by Fluoxetine, Paroxetine,
Thieme-connect - Abstract
... stronger than the known mechanism-based inhibitor, paroxetine (a positive control). Thus, 15 and 17 are potent mechanism-based inhibitors of CYP2D6. ...
www.thieme-connect.com/ejournals/abstract/plantamedica/doi/... - Similar pages
Mechanism-Based Inhibition of Human Liver Microsomal Cytochrome P450 2D6 (CYP2D6) by Alkamides of Piper nigrum
Subehan1, Tepy Usia1, Shigetoshi Kadota1, Yasuhiro Tezuka1,2
1 Institute of Natural Medicine, University of Toyama, Toyama, Japan
2 21st Century COE Program, University of Toyama, Toyama, Japan
Abstract
Nineteen alkamides isolated from Piper nigrum L. were tested for their mechanism-based inhibition on human liver microsomal dextromethorphan O-demethylation activity, a prototype marker for cytochrome P450 2D6 (CYP2D6). All compounds increased their inhibitory activity with increasing preincubation time. Among them, 15 and 17 showed more than 50 % decrease of the CYP2D6 residual activity after 20 min preincubation. Further investigations on 15 and 17 showed that the characteristic time- and concentration-dependent inhibition, which required a catalytic step with NADPH, was not protected by nucleophiles, and was decreased by the presence of a competitive inhibitor. The kinetic parameters for inactivation (kinact and KI) were 0.028 min-1 and 0.23 μM for 15 and 0.064 min-1 and 0.71 μM for 17, respectively, which were stronger than the known mechanism-based inhibitor, paroxetine (a positive control). Thus, 15 and 17 are potent mechanism-based inhibitors of CYP2D6.
--------------------------------------------------
Note added at 4 hrs (2006-11-05 14:08:20 GMT)
--------------------------------------------------
Please note: As far as I understand, the study points out that Paroxetine IS a potent mechanism-based inhibitor, as opposed to DSV-233.
4 KudoZ points awarded for this answer.
Comment: "Thanks Liz. You are spot on with your assumption - paroxetine was used as the positive control in these studies as it is potent inhibitor. "Mechanism-based inhibitor" - also agree. Many thanks! "
16 mins
paroxetine that proved to be a potent CYP2D6 inhibitor
Your interpretation is correct, the original sounds redundant.
The SSRI antidepressant paroxetine is a potent CYP2D6 inhibitor, Adam.
See these references:
http://www.mdma.net/metabolism/p4502d6.html
http://jncicancerspectrum.oxfordjournals.org/cgi/content/ful...
In our study, we separated, purified, and identified the tamoxifen metabolite 4-hydroxy-N-desmethyl-tamoxifen, which we designated endoxifen, as a metabolite whose concentration was decreased when patients were coprescribed paroxetine, a CYP2D6 inhibitor.
Several publications state that it's a potent inhibitor of CYP2D6, however you need subscriptions to have access to that material. Ex.: http://www.psychiatry.jwatch.org/cgi/content/full/2003/507/2
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Note added at 19 mins (2006-11-05 10:17:20 GMT)
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www.blackwell-synergy.com/doi/pdf/10.1111/j.1365-2125.2006....
Here goes an FDA reference:
http://www.fda.gov/cder/Offices/OCPB/Flockhart2005.pdf
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Note added at 22 mins (2006-11-05 10:19:52 GMT)
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Sorry, adapting the sentence to the rest of the context...
Paroxetine, the positive control, proved to be a potent inhibitor of CYP2D6.
The SSRI antidepressant paroxetine is a potent CYP2D6 inhibitor, Adam.
See these references:
http://www.mdma.net/metabolism/p4502d6.html
http://jncicancerspectrum.oxfordjournals.org/cgi/content/ful...
In our study, we separated, purified, and identified the tamoxifen metabolite 4-hydroxy-N-desmethyl-tamoxifen, which we designated endoxifen, as a metabolite whose concentration was decreased when patients were coprescribed paroxetine, a CYP2D6 inhibitor.
Several publications state that it's a potent inhibitor of CYP2D6, however you need subscriptions to have access to that material. Ex.: http://www.psychiatry.jwatch.org/cgi/content/full/2003/507/2
--------------------------------------------------
Note added at 19 mins (2006-11-05 10:17:20 GMT)
--------------------------------------------------
www.blackwell-synergy.com/doi/pdf/10.1111/j.1365-2125.2006....
Here goes an FDA reference:
http://www.fda.gov/cder/Offices/OCPB/Flockhart2005.pdf
--------------------------------------------------
Note added at 22 mins (2006-11-05 10:19:52 GMT)
--------------------------------------------------
Sorry, adapting the sentence to the rest of the context...
Paroxetine, the positive control, proved to be a potent inhibitor of CYP2D6.
22 mins
Clare Macnamara
Native in English
Fast, efficient and intuitive.
Native in: English 
Works in: Spanish to English, French to English
Related KudoZ points
:
12
potent inhibitor of CYP2D6 (activity)
Hi Adam,
I share your opinion about the original. My suggestion is based on the suspicion that paroxetine isn't an inhibitor of the inhibition mechanism, but of CYP2D6 itself, or of CYP2D6 activity. Not sure though!
Apparent mechanism-based inhibition of human CYP2D6 in vitro by ... - [ Traduzca esta página ]
Paroxetine, a selective serotonin reuptake inhibitor, is a potent inhibitor of cytochrome P450 2D6 (CYP2D6) activity, but the mechanism of inhibition is not ...
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubM...
Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the ... - [ Traduzca esta página ]
Paroxetine is a very potent inhibitor of CYP2D6. The objective of this study was to investigate the influence of paroxetine pretreatment on the ...
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubM...
Psychiatric Drugs: Paroxetine (Paxil, Paxil CR) - [ Traduzca esta página ]
A. Paroxetine is a potent inhibitor of the liver enzyme, CYP2D6. Use caution when combining with TCAs or antiarrhythmics. Can also elevated levels of some ...
psychiatric-drugs.org/2006/06/paroxetine_paxil_paxil_cr.html - 14k -
I share your opinion about the original. My suggestion is based on the suspicion that paroxetine isn't an inhibitor of the inhibition mechanism, but of CYP2D6 itself, or of CYP2D6 activity. Not sure though!
Apparent mechanism-based inhibition of human CYP2D6 in vitro by ... - [ Traduzca esta página ]
Paroxetine, a selective serotonin reuptake inhibitor, is a potent inhibitor of cytochrome P450 2D6 (CYP2D6) activity, but the mechanism of inhibition is not ...
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubM...
Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the ... - [ Traduzca esta página ]
Paroxetine is a very potent inhibitor of CYP2D6. The objective of this study was to investigate the influence of paroxetine pretreatment on the ...
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubM...
Psychiatric Drugs: Paroxetine (Paxil, Paxil CR) - [ Traduzca esta página ]
A. Paroxetine is a potent inhibitor of the liver enzyme, CYP2D6. Use caution when combining with TCAs or antiarrhythmics. Can also elevated levels of some ...
psychiatric-drugs.org/2006/06/paroxetine_paxil_paxil_cr.html - 14k -
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