• N&PD Moderators: Skorpio | thegreenhand

Enzymes (eg CYP2D6/CYP3A4) and Inhibitors/Inducers

Cimetidine inhibits CYP2D6, so if you're using it in conjunction with a codeine derivative, that's a step backwards
 
...I see, there is the need to post the 2nd here, too:

2D6 inhibitors: Amiodarone, Cimetidine, Citalopram, Clomipramine, Desipramine, Fluoxetine, Fluphenzine, Fluvoxamine, Haloperidol, Methadone, Mibefradil, Moclobemide, Norfluoxetine, Paroxetine, Perphenazine, Propafenone, Quinidine, Ritonavir, Sertraline , Thioridazine

2D6 substrates: Amitripyline, Bisoprolol, Captopril, Cilostazol , Chlorpheniramine, Chlorpromazine, Citalopram, Clomipramine, Clozapine, Codeine, Cyclobenzaprine, Desipramine, Dexfenfluramine, Dextromethorphan , Donepezil, Doxepin, Encainide, Ethylmorphine, Fenfluramine, Flecainide, Fluoxetine, Fluphenazine, Haloperidol, Hydrocodone, Imipramine, Indoramin, Labetalol, Lidocaine, Loratadine, Maprotiline, (R)-methadone, Meperidine, , Methadone, Methamphetamine, Metoprolol, Mexiletine, Morphine, Nefazodone, Nelfinavir, Nortriptyline, Ondansetron, Omeprazole, Oxycodone, Paclitaxel, Paroxetine, Perphenazine, Phenformin, Propafenone, Propranolol, Retinoic acid, Quinidine, Risperidone, Ritonavir, RU486, Tamoxifen, Testosterone, Timolol, Tramadol, Trazodone, Trifluperidol, Trimipramine, Venlafaxine, Vinblastine

2D6 inducer: Carbamazepine, Phenobarbital, Phenytoin, Rifampin, Ritonavir
 
@Jamshyd:

Chronic smoking is thought to raise levels of CYP2D6, 2E4, 2B6 in the brain. In general, nicotine raises levels of 2B- and 2D-enzymes in the brain, while it raises 2E1-levels in brain AND liver. Smoking also raised CYP1A2-levels in the liver in animal models (hamster, rat), also 2A8 (in hamster! ...these equal 2A6 in humans). The 1A2-activation could also be observed with humans, what confirms the studies.

I guess, there are more CYPs involved in smoking but these are the most mentioned.

PEACE! Murphy
 
Hi,

thought I'd add this in (sorry if its in the wrong place)

Both buprenorphine and nor-buprenorphine are inhibitors too of both CYP2D6 and 3A4.

Bupe is a strong in-vitro inhibitor (but not a good substrate) and nor-bupe is a moderate in-vitro inhibitor of 2D6.
 
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^
I'll add that buprenorphine has higher affinity to the mu receptor than norbuprenorphine , however norbuprenorphine seems to be a full agonist and also has ahigh affinity to the ORL-receptor , so it might play a role especially in low doses of buprenorphine (let's say below 2 mg sl)

In fact some people experience a short period of withdrawal after taking their dose in the morning because of the norbupe getting knocked off the receptors by the bupe
 
if you take Quercetin (CYP3A4 inhibitor)
would that render contraceptive pill useless? considering the pill requires that enzyme to metabolise?

also what will happen to the high of MDMA when taken with CYP3A4 inhibitor?
 
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^
Yup, I remember the Ki values@MOR for bupe is 0.7nM and for nor-bupe, 0.8nM
 
Advanc3d said:
also what will happen to the high of MDMA when taken with CYP3A4 inhibitor?


MDMA is first metabolized by CYP3A4 (N-demethylation) to MDA.
Both are then metabolized by CYP2D6.

There are other enzymes involved in this, although 2D6 is the primary enzyme for metabolizing MDMA. I suspect taking MDMA with a 3A4 inhibitor may not make that much of a difference.
 
aj1976 said:
MDMA is first metabolized by CYP3A4 (N-demethylation) to MDA.
Both are then metabolized by CYP2D6.

There are other enzymes involved in this, although 2D6 is the primary enzyme for metabolizing MDMA. I suspect taking MDMA with a 3A4 inhibitor may not make that much of a difference.

MDA is neurotoxic metabolite of MDMA though, guessing inhibiting its production is a plus?
i would i thought CYP3A4 inhibitation with MDMA will make the high last longer


actually, i just picked this up from wikipedia

Because the enzyme CYP2D6 is deficient or totally absent in some people[80], it was once hypothesized that these people might have elevated risk when taking MDMA. However, there is still no evidence for this theory and available evidence argues against it.[81] It is now thought that the contribution of CYP2D6 to MDMA metabolism in humans is less than 30% of the metabolism. Indeed, an individual lacking CYP2D6 was given MDMA in a controlled clinical setting and a larger study gave MDMA to healthy volunteers after inhibiting CYP2D6 with paroxetine. Lack of the enzyme caused a modest increase in drug exposure and decreases in some metabolites, but physical effects did not appear appreciably elevated. While there is little or no evidence that low CYP2D6 activity increases risks from MDMA, it is likely that MDMA-induced CYP2D inhibition will increase risk of those prescription drugs that are metabolized by this enzyme. MDMA-induced CYP2D inhibition appears to last for up to a week after MDMA exposure
 
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Advanc3d said:
if you take Quercetin (CYP3A4 inhibitor)
would that render contraceptive pill useless? considering the pill requires that enzyme to metabolise?
I don't know if oral contraceptives are metabolized through this pathway but IF SO, then:
The contraceptive pill wouldn't be totally useless. But the possibility of a failure of protection is increased. The term "to render it useless" implies for me the total failure with the majority of affected women. This is not the case here. It is rather like a higher percentage of pregnancies occur when taking respective CAP-inhibitors.

In my place, Hypericum perforatum (ENG: St. John's wort; GER: Johanniskraut; FR: Millepertuis perforé) is a light OTC-antidepressant with exactly this side-effect. Ouch!:\

Peace! Murphy
 
^^Hypericum perforatum is a CYP3A4 inducer not inhibitor, no?

Peace
J
 
Indeed it is. This means the contraceptive's half life is significantly reduced, so plasma level of it are decreased, and contraceptive reliability falls. If however it were a prodrug then yeah we'd be concerned with inhibition more.
 
Thought so, as a long term user of Xanax for panic disorder i started to use St. John's wort to se if it would help. Nope, had to increase my Xanax dose by 50%.
J
 
umm???

guys so i have cilostazon and chlorpramazine i wanna do it wit suboxone ??? so what one do i use to make it stronger?? im confused=D
 
no one will prob ever look at this but ne way the cilostazol is for poor blood circulation kk and the promazine is a old drug from the 50s so how are there gonna do ne thingf to suboxone? or any opiate for that matter???? pls teach me how lol
 
A molecule can act as both an inhibitor and modification product for an enzyme if it has a strong binding capacity for the binding pocket, but a reduced ability to undergo the reaction mechanism the enzyme catalyzes. Hence it is an inhibitor because it is slow to react with the enzyme compared to other substrates, and this can be readily detected in vitro with or without sufficiently detailed analysis to figure out what is truly going on.

I believe the OP was asking about this as well? I don't know of any other way for it to happen, although I am not directly familiar with the data for codeine and other molecules on this issue. It is an interesting concept however...
 
I'm on Metronidazole as of today for an infected wisdom tooth, taking it three times a day, but I would like to drop 1 or 2 pills at a rave this Saturday...

Could anyone explain the risks involved for me? Would it have a serious effect on my treatment if I didn't take any doses for all of Saturday day, but start again on sunday morning / when coming down?

Lets say I take my last dose at 6 - 7 PM on the Friday, and drop pills at the rave at say 1 - 2 am, and have Sunday's first dose of Metronidazole at 8am?
 
BUMP BUMP BUMP//// Now i was hoping that people could talk to me about how all this information relates to suboxone does anyone have any information of BUPE and how to increase the level Of NOR BUPE and if this is safe extra for someone who is on a mataince of bupe and takes it daily tryin to cop a free high ???
 
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