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The Large and Nifty Not-quite-advanced Drug Chemistry, Pharmacology and More Thread

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^you can't confirm id just with UV and a HPLC retention time unless either

you ran the HPLC conditions, flow, gradient, column which are the same as it has been listed somewhere else there are plenty of HPLC refs for ID of benzodiazepines, you would also have to run either an internal standard in your sample or a separate standard because of dead volume etc in the machine
or
Unless you have a reference sample to run under the same conditions the id by retention time would be possible.

A quick look shows there are also two materials here one eluting later but partially co-eluting with the major peak.

MS would be better.

V
 
temazepam metabolization

I have a question for the pharmacology buffs (you all know who you are ;)) - why is it that cimetidine and/or WGFJ work on most benzodiazepines, but not temazepam?

How is temazepam metabolized? Why are its metabolites inactive?

Is there a way to prevent temazepam from being metabolized as quickly as it normally is?

Thank you in advance. I remember reading on wiki that temazepam isn't boosted by cimetidine or WGFJ at all.
 
Hey guys, I am an avid codeine user and have wondered something for a while. I know CYP2D6 inhibitors slow down the metabolism of codeine and while reducing the strength of a dose also increase the duration. Codeine has a 'ceiling dose' of 400-500mg.

What I wondered is if you could inhibit CYP2D6 to a reasonable level and then take 800-1000mg of codeine and achieve peak effects from the ceiling dose but with twice the standard duration? I love my codeine but it just doesn't last long enough, this idea seems like it could work to me but I am nowhere near as knowledgable as the posters over here in ADD.

If anybody could shed some light on this I would appreciate it very much. :) Thanks!
 
Captain.Heroin said:
I have a question for the pharmacology buffs (you all know who you are ;)) - why is it that cimetidine and/or WGFJ work on most benzodiazepines, but not temazepam?

How is temazepam metabolized? Why are its metabolites inactive?

Is there a way to prevent temazepam from being metabolized as quickly as it normally is?

Thank you in advance. I remember reading on wiki that temazepam isn't boosted by cimetidine or WGFJ at all.
Click to expand...

It's metabolized by conjugation and demethylation. One metabolite, N-desmethyl temazepam, is only present in small quantities (7% I've read).
Not sure if they're inactive or not though I'm afraid :\
 
Yer quite welcome :) I've had a good look but haven't found much info at all which is silly. It's been around since the late 60's and has been in use since then.
You'd imagine there'd be extensive research into such things :?
 
monstanoodle said:
Yer quite welcome :) I've had a good look but haven't found much info at all which is silly. It's been around since the late 60's and has been in use since then.
You'd imagine there'd be extensive research into such things :?
Click to expand...

There is.

CYP3A4 generally does 2 things to this family of benzos: it N-demethyates them and it 3-hydroxylyzes them.

Here are temazepam (L) and oxazepam (R):
200px-Temazepam.svg.png
,
dl274.png


Oxazepam is N-desmethyl temazepam (the 7% metabolite you mentioned).

As you can see, they both have an -OH on the 3 carbon. This -OH means there's very little for CYP3A4 to do. The body then kicks enzymes called glucuronyl transferases into action so that the -OH becomes -O-glucuronide (basically it replaces the H with a glucose unit, unless I'm botching the stereochemistry). This latter product is definitely inactive and eventually pissed away.

Extending the duration of temazepam: I'm guessing there are 2 possible routes:

1) Induce CYP3A4. This is possibly going to weaken the experience, but it's worth a try.
2) Inhibit glucuronidation. There's a thread on this somewhere. Search ADD for NAPROXEN STATIN (I think that'll get you tthere).
 
Are both enantiomers of temazepam equally active does anyone know?
 
seep said:
Are both enantiomers of temazepam equally active does anyone know?
Click to expand...

No idea. However I think the one used in pharmaceuticals is the one where the bond to the OH goes downward from the diazepine ring if the molecule is looked at as in the above post (cba to figure out if it's R or S)
 
According to chemspider it's racemic. This is the correct drawing:

ImagesHandler.ashx


For R, the -OH projects out of the page.
 
This thread is spectacular in comparing the structures of psychedelics- mainly showing that the 5-methoxy group on psychedelic phenethylamines is analogous to the indole nitrogen, and the 2-methoxy is analogous to the 5-hydroxy in serotonin, and how it all fits into LSD.

figure_005.jpg

The figure above shows psilocin. If one were to create the phenethylamine analogue of psilocin, it wouldn't be BOD and it shouldn't even be a phenethylamine. Here is what it should be:
9fb3bcf453.png


I get the feeling that if somebody actually made this compound, it would be either a complete success or a complete failure (no activity). But then again, who knows.
 
Yeah, that is definitely similar, except the non-methoxy ether in ORG doesn't overlay over the 4-hydroxy in psilocin (and the ORG methoxy ether isn't overlaying the 4-hydroxy, it's overlaying the nitrogen in the indole part of psilocin). Yet now I am even more certain that the compound I suggested is active.

But it's interesting, thanks. What exactly was F&B most incorrect about?
 
Does anyone know of where I can find some images of fMRI, PET, SPECT or similar scans of people on serotonergic psychedelics? Any help would be greatly appreciated. Been trying to use google images, but no real luck. For some reason, regardless of what else I type in, anything with LSD gets mostly results that are of blotter paper & hippies
 
But it's interesting, thanks. What exactly was F&B most incorrect about?
Click to expand...

one quote answers another...

Hammilton said:
Tryptamines and Phenethylamines do not bind the same way. When it comes to 5HT2a binding, it's a mistake to look for homologous positions, because they're not interacting with the receptor in the same way.
Click to expand...
 
surrеalist;8049027 said:
Yeah, that is definitely similar, except the non-methoxy ether in ORG doesn't overlay over the 4-hydroxy in psilocin (and the ORG methoxy ether isn't overlaying the 4-hydroxy, it's overlaying the nitrogen in the indole part of psilocin).
Click to expand...

I'm not saying that these compounds overlay, cuz I haven't done the comparison. However, they're pretty close. First, remember that 5-MeO-DMT has a greater affinity in general for the serotonin receptors than does 4-MeO-DMT. So, the methoxy in the ORG compound and the methoxy group meta to the bromine in your proposed compound would overlay the methoxy in 5-MeO-DMT. Then the amine (I'd propose making it a secondary or tertiary amine) in your compound would overlay somewhat closely with the amine in the ORG compound and the tryptamines.

You can figure out the rest of the similarities. It's worth noting that the ORG compound has a higher affinity for the 5-HT2C receptors, and it has a low efficacy at all of the serotonin receptors. It's also worth noting that 2-bromo-LSD isn't a psychedelic although it has affinity for the 5-HT2A receptor.
 
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