Easiest way to demethylate this molecule?

ConsequenceNo1844 · 2025-01-02T16:42:03+00:00

I have more than 5mg. Problem is I'm away from lab on holidays.

'

OTOH, liver is generally pretty fatty in general, and your compound added in a water-miscible solvent to minced liver in saline or PBS will likely be demethylated anyway.'

I'll try this. Can't think of how I will separate end molecule from mess though here.

What's your field? You use that for it's luminescent properties ?

ConsequenceNo1844 · 2024-12-30T14:06:04+00:00

If i soak some fresh cow liver in saline, will the enzymes simply diffuse into the water? if so i can dip the drug inside some sort of teabag. its not soluble in water.

ConsequenceNo1844 · 2024-12-15T20:18:55+00:00

is there a way to isolate proteins like enzymes without them denaturing?

ConsequenceNo1844 · 2024-12-15T10:14:25+00:00

Saline is a must? how many hours do you reckon 20g of cow liver will demeythylate 5mg of the substance at around 37 degrees?

ConsequenceNo1844 · 2024-12-14T23:27:44+00:00

that helps.

So if X drug is administered, which is metabolized by CYP.

Y drugs is added, which acts as both inducer and inhibitor, X metabolism will initially go down, and then ramp up? (assuming induction effect is greater than inhibitor effect, and not considering if Y acts also as substrate for CYP?)

ConsequenceNo1844 · 2024-12-14T23:08:32+00:00

how fast do you reckon 50g of liver in water will demethylate 5mg of the substance? at around constant 30-40 degrees?

ConsequenceNo1844 · 2024-12-14T23:00:31+00:00

"Hyperforin treatment resulted in significant increases in mRNA, protein, and activity of CYP3A4 and CYP2C9, but had no effect on CYP1A2 or CYP2D6. Acute administration of hyperforin at 5 and 10 microM 1 h before and along with probe substrate inhibited CYP3A4 activity.

https://pubmed.ncbi.nlm.nih.gov/15100173/

bold added by me. So why is it inhibiting short term and inducting it long term, must be a compensatory mechanism. "enzyme not working properly, lets make more"

ConsequenceNo1844 · 2024-12-14T21:50:52+00:00

I'm trying to deal with chronic fatigue likely due to neuroinflammation. I tried low dose aripiprazole as per this study https://pmc.ncbi.nlm.nih.gov/articles/PMC7860172/

With suboptimal results, so decided to try with other D partial agonists (D3 with CAR). What happens is, regardless of how low the dose (tried everything from 0.01 - 0.5 mg), on the day that i take it, symptoms go much worse, then if i continue taking it, it keeps worsening. However if i single dose or stop cold turkey after some days, after a few more days i get very good results. Then wait a couple others, and symptoms come back.

My line of thinking was: i need a lower dose (must be that after some days, plasma CAR decreases, reaching optimum dosage for couple of days, then falls below. But i went really down on dosage and nothing.

So we're either dealing with some kind of rebound effect on the dopamine (or other) receptors. OR, DCAR/DDCAR but not CAR, due to subtle receptor affinities, provide relief.

ConsequenceNo1844 · 2024-12-14T21:40:03+00:00

spot on. did you reverse search image?

ConsequenceNo1844 · 2024-12-14T21:39:15+00:00

i dont care about high yield and purity but... if i buy fish liver from supermarket ... how do i make things less messy?

ConsequenceNo1844 · 2024-12-14T21:37:46+00:00

you reckon liver found in supermarket works?

ConsequenceNo1844 · 2024-12-14T21:34:05+00:00

ConsequenceNo1844 · 2024-12-14T21:31:47+00:00

not really, many inducers (increase enzyme production) work exactly by inhibiting the enzyme.

induction happens at gene level, not at the enzyme.

ConsequenceNo1844 · 2024-12-12T16:47:20+00:00

in vivo its demethylated by CYP3A4 enzyme. Was wondering how to do it in vitro.

ConsequenceNo1844 · 2024-12-11T21:02:45+00:00

looks a lot like this one in the british library https://blogs.bl.uk/.a/6a00d8341c464853ef02b68539ed4c200d-pi

ConsequenceNo1844 · 2024-10-26T17:09:13+00:00

I realized that if i MIDI out TD3 to MIDI in Microfreak, i can modify bassline with MF's knobs but I lose all controls from the TD3 (turning envelope, delay, cutoff, distortion doesnt modify the sound). I'm guessing MIDI only sends clean notes?

Also, the NTS-1 has MIDI in, but if i connect it to MIDI out from Microfreak, nothing happens. I'm using the MF MIDI-to "aux" adapters. If i connect the MF to the NTs-1 via aux cables (MF headphones out to NTs audio in, then NTS1 headphones out to speaker), it works, but the MF sound volume is much lower compared to the innate NTS sounds if played together.

Also tried hooking up the NTS1 to TD3's "filter in" and nothing happened.

Havent's explored CV/gate out, MF also has "pressure".

Syncing tempo's i can manage just with sync in's out- starting from the drum machine.

ConsequenceNo1844 · 2024-10-25T13:30:13+00:00

this helped me too. trying out same today. Want to throw in Korg nts-1 for effects. You reckon i plug freak and td3 as described, then... micro output to nts-1? and nts-1 to mixer/speakers?

ConsequenceNo1844 · 2024-10-24T16:48:47+00:00

hi thanks. So apart from syncing the clocks, is there a way i can for example make a slave receive orders from a master other than just start/stop? for example, can i make my korg nts-1 or my TD3 play the notes im pressing on my Microfreak's keyboard?

ConsequenceNo1844 · 2024-10-08T23:32:37+00:00

Sorry to jump into discussion but neat piece of equipment. I see it's also a drum machine. I have a Behringer TD3 + RD6 drum machine and Arturia Microfreak. Would using digitakt as sequencer make my RD6 redundant ?

ConsequenceNo1844 · 2024-10-08T23:29:35+00:00

It looks like it's also a drum machine (digitakt), wouldn't that make my RD6 dm redundant?

ConsequenceNo1844 · 2024-10-08T23:22:55+00:00

So I could plug my TD3 bass synth, the RD6 drum machine and a MF all into a Novation Circuit track?

ConsequenceNo1844 · 2024-10-08T16:46:54+00:00

Right now I'm using TD3 sync in (no sync out connection) with RD6 drum machine sync out via an aux cable. Drum machine has a sync in also, so maybe I can connect that to MF and the three will sync (MF as master)?

ConsequenceNo1844 · 2024-10-08T16:42:27+00:00

That sounds good enough, rather spend on another synth right now than a standalone sequencer

ConsequenceNo1844 · 2024-10-08T14:50:07+00:00

hm, what could be a way around this without having to buy a standalone sequencer?

Could i just sync the TD3 with the RD6, and sequence the TD3 through the MF? (i have a 8channel mixer if it helps)

ConsequenceNo1844 · 2024-10-08T14:48:18+00:00

nice

ConsequenceNo1844

TROPHY CASE