Benzos Tagamet and clonazepam

[THE_REAL_OBLIVION]

I've read extensively about benzos in my life, was scripted clonazepam first of all, then tapered to valium and attained a 66% reduction in daily benzo consumption, except when I take one of the mere 15 .5mg (i'll have to have that fixed, need 1mg at least) for when I feel panic arising. My neurologist has scripted me topamax (which I will not take) and clonazepam 1mg bid once again for my migraines "NOS". Back then I could never test it because Tagamet has been prescription only since a good decade in .ca . I got a Rx for 600mg cimetidine horsepills this year though and I wonder, does tagamet not do anything to clonazepam unlike the 2 other benzos I take ? It doesn't have active metabolites which I think is the point of blocking enzymes with tagamet, so that the metabolites of valium and xanax get larger plasma levels.

tl;dr Tagamet and Rivotril....does it work like with most other benzos ?

 

[Xerolad]

Great question T_R_O!

Cimetidine is pure gold as a drug potentiator. It has few side effects on its own, and can dramatically increase plasma levels of a huge variety of drugs by reducing the metabolic activity of several CYP450 enzymes: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4.

The point of using potentiators like cimetidine is not to increase the plasma levels of active metabolites, but rather to prevent the conversion of the parent drug into its inactive metabolites.

To answer your specific question, clonazepam has no active metabolites, and is therefore a great candidate for attemps to prolong and intensify its effects by increasing the AUC (area under the plasma concentration vs. time curve) of the parent drug with enzyme-blocking potentiators. Happily, it is metabolized by CYP2C19 and CYP3A4, which are blocked by cimetidine! Try 800 mg cimetidine plus your ususal dose of clonazepam to assess the difference in effects.

Another great potentiator, BTW, is grapefruit/grapefruit juice. For example, grapefruit juice increases oxycodone AUC 1.5- to 2.3-fold by blocking CYP3A4, and significantly prolongs its half-life. This means that if grapefruit juice is consumed 30-60 minutes before oxycodone the effects are greater and last longer. The "grapefruit effect" persists to some degree for up to 3 days. Another 3A4 substrate is alprazolam (although the resulting metabolite is also active). The number of other drugs metabolized by CYP3A4 is too long to list here!

Cimetidine and grapefruit juice should have their own "Big and Dandy Megathread" for people to post their experimentations with these potentiators other stuff. Like MAOI's, these potentiators have the potential to lead to unpredictable effects not normally seen when the parent drugs are metabolized normally, and could result in fatal overdose if used unwisely. Start low and go slow.

Hope this is of some use to you.

 

[weekend addiction]

Great post^ I can't add anything to that other than I use it quite often its OTC in the US.

 

[THE_REAL_OBLIVION]

Well I have a script for 600mg tagamets, they aren't scored and are HARD as all hell, I assume these work (the indeed did work on methadone when I was still on that shit). But thanks for the info, it is something I never fully understood, I remember how grapefruit juice didn't have much effect on clonazepam while it had MASSIVE effect on Alprazolam, nitrazepam and to a lesser degree diazepam.

 

[Xerolad]

T_R_O, I think clonazepam is metabolized primarily by CYP2C19, and to a much lesser extent by CYP3A4. GFJ mostly blocks CYP3A4, so it wouldn't have too much effect on clonazepam.

 

[THE_REAL_OBLIVION]

Yeah, just what I thought, anyways, the mere 15 .5mg clonies I had are gone...like my xanax...i'm waiting for my etizolam now...el sigh. I do get a refill for valium on the 6th though...hopefully the etiz makes its way here before.