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The following message was posted to: PharmPK
Dear group,
I'm working on in-vitro-studies to see influences of designer drugs (like
MDMA, "XTC", and Amphetamine) on the metabolism of THC, the active component
of cannabis. Working with human hepatic microsomes, THC is metabolized
mainly to Hydroxy-THC (by CYP2C9), but also to a lot of other metabolites.
If I start an THC-metabolism-assay with MDMA, I found out that at high MDMA
concentrations (300=B5M, pre-incubated 2 =BD min) there is a significant
increase of Hydroxy-THC be formed (we did GC-MS analysis). At lower MDMA
concentration levels (0.3; 3.0; 30=B5M), there is no increase; the amound of
formed Hydroxy-THC is the same as without addition of MDMA.
We've got a hint to have co-oxygenation involving free radicals, which was
observed with benzo(a)pyrene and its 7,8-dihydrodiol, but it seems not to be
the case in the THC-Metabolism study with MDMA.
Does anybody has an explanation for this kind of "induction"??
Thank you very very much
Stefan Steinmeyer
Stefan Steinmeyer
University of Saarland
Institute of Legal Medicine, Toxicology
Building 42
D-66421 Homburg/Saar
Germany
Tel.: ++49-6841/1626315
=46ax.: ++49-6841/1626314
E-Mail: rmsste.-at-.med-rz.uni-sb.de
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The following message was posted to: PharmPK
Stefan:
Since you excluded co-oxygenation, the alternative reasonable
explanation for increased enzymatic activity with a poorly soluble in
water substrate (THC) could be - increased solubility.
Check if MDMA does not produce some kind of water-soluble
complexes with THC and if there is no "detergent-like" effect of MDMA
salt in your system (I guess, it is pH-buffered, otherwise you need
to control pH with and without 0.3 mM MDMA).
Moreover, I would not call this almost immediate effect an
"induction". A real induction in the intact cellular systems needs
some time (protein biosynthesis needs to crank).
Best wishes.
Janusz Z. Byczkowski, Ph.D.,D.Sc.,D.A.B.T.
Consultant
212 N. Central Ave.
Fairborn, OH 45324
voice (937)878-5531
office (614)644-3070
Secure fax (513)766-2003 x 3064
e-mail januszb.aaa.AOL.com
homepage: http://members.aol.com/JanuszB/index.html
JZB Consulting web site: http://members.aol.com/JanuszB/consult.htm
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