• N&PD Moderators: Skorpio | thegreenhand

  • Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

Hard to Find paper - Anyone?

C

clubcard

Bluelighter
Joined
Apr 12, 2013
Messages
1,483
Hi,
I have tried everything to obtain:


Pharmazie. 1982 Jan;37(1):69.

[Is pyrithyldione (Benedorm) an enzyme inducer (author's transl)]

by H H Borchert, S Schuster, H Lipfert, S Pfeifer

PMID: 7071114


Now, Sci-Hub is supposed to accept PMIDs but I have never got it to work.

The reason why this is so valuable is that the glutethimide metabolite, 4-hydroxy glutethimide can undergo dehydration leading to an alkene and If pyrithyldione is also an enzyme inducer, we have a QSAR for the VERY hard to find CYP2D6 inducers. I am more than happy to credit whoever posts or otherwise conveys the results of the papers because IF it is the alkene then the amount needed for induction is very SMALL. I am aware that 4-hydroxy flutethimide prevents gluconation of morphine thus increasing duration BUT truthfully, a safe, effective CYP2D6 inducer is important the medicine, not just for us taking it with codeine to get a heroin-like high.
 
That paper is pre digitalisation, Pharmazie is digital 2003 onwards so it's a trip to the library and a photocopier job. Most academic libraries don't seem to hold that journal in paper form. You might want to order a copy from the British Library in London through your local library.

CYP2D6 poor metabolizers are annoying from a tox perspective. Are you sure you can overcome it with an inducer because the poor metabolizers have a really poor version of the enzyme and some one in 12 in western populations have no functional enzyme at all, which makes inducing it a lttle tricky.

Is it true gluthemide causes weird hormonal side effects, like moobs and adrenal insufficiency or something like that? I can't be bothered to look it up.
 
Frost, J., Løkken, T. N., Helland, A., Nordrum, I. S., & Slørdal, L. (2016).
Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, norcodeine, morphine and morphine glucuronides in a series of codeine-related deaths. Forensic Science International, 262, 128–137. doi:10.1016/j.forsciint.2016.02.051

It would appear that the CYP2D6 induced by glutethamide results in up to around 50% of the codeine is metabolised to morphine or M6G. Pyrithyldione only converta about 20% (and at high doses). The next thing to discover if which of the glutethimide isomers is responsible... we are getting there, slowly.
 

www.ncbi.nlm.nih.gov

Linking Aromatic Hydroxy Metabolic Functionalization of Drug Molecules to Structure and Pharmacologic Activity

Drug functionalization through the formation of hydrophilic groups is the norm in the phase I metabolism of drugs for the modification of drug action. The reactions involved are mainly oxidative, catalyzed mostly by cytochrome P450 (CYP) isoenzymes. The ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

www.pnas.org

Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450

Cytochrome P450 enzymes play key roles in the metabolism of the majority of drugs. Improved models for prediction of likely metabolites will contribute to drug development. In this work, two possible metabolic routes (aromatic carbon oxidation and O-demethylation) of dextromethorphan are...
www.pnas.org www.pnas.org


The Journal of Biological Chemistry, 08 Jul 2015, 290(33):20200-20210
DOI: 10.1074/jbc.m115.665331 PMID: 26157146 PMCID: PMC4536429
 
You must log in or register to reply here.
Top