H1 receptor competition?

[bunge]

Hi, hope you guys can chuck me a few nuggets of wisdom and thanks in advance. My doctor has prescribed me hydroxyzine to take for anxiety alongside my daily mirtazapine. What im wordering is although they both act at the H1 receptor, which one is more potent? Or will they work to increase the anti-histamine action of each one? The doctor seemed fairly clueless but aaid she thinks it will just lead to a bit more sedation which is absolutely fine by me... so long as it isnt dangerous of course.

 

[Wizzle]

Well, if you take them together (mirtazapine is usually taken at night), the hydroxyzine is gonna do jack shit. Mirtazapine has an extremely high affinity for H1 and is actually an inverse agonist... Pharmacokinetics are tricky, so it might or might not be usefull to take hydroxyzine during the day and mirtazapine at night. Not sure.

What dosages are you using?

 

[bunge]

My thoughts ran the same way pretty much with the affinity of mirtazapine, so the plan was to take the hydroxyzine about 3 hours before the mirtazapine and then the mirtazapine just before bed as usual. I take 45mg of mirtazapine and im stable at that dose for about 2-3 months. Im scripted to take 25mg of hydrozine but feel that may not be enough so will more then likely move up to 50mg quickly.

 

[sekio]

the hydroxyzine is gonna do jack shit.

Hydroxyzine and mirtazapine have about the same affinity for the H1 histamine receptor, so they should just potentiate each other's effects. Don't expect miracles, but you should see more happen than "jack shit".
It does actually have actions apart from an antihistamine (blocks a few serotonin receptors) that play a role in the anxiolytic effects.

 

[bunge]

Thanks for the info guys, seems like it might be an interesting experiment to see how these meds compare for potency and how well they work together (at least ill find it interesting.lol). Sekio, I dont suppose you know which of the serotonin receptors hydroxyzine effects ? Or maybe point me the right way to find that info for myself. Thanks again for your time. :-D

 

[sekio]

http://en.wikipedia.org/wiki/Hydroxyzine#Pharmacology
http://en.wikipedia.org/wiki/Mirtazapine#Pharmacology

Suprisingly, Wikipedia is usually pretty good for this kind of stuff. At least for the well-researched drugs.
Hydroxyzine out-competes mirtazepine at all of its targets (a1 adrenergic, 5ht2a, D2) except H1. So it should still be an effective anxiolytic.

(If you haven't seen them ebfore, Ki's are a measure of how much drug it takes to displace a radioactive ligand from a protien. Basically, they are a measure of how strongly a drug binds. (not neccesarily its activity - that's usually given as an EC50, or Effective Concentration for 50% activation.) In both Ki and EC50s though, the numbers are given in moles (usually millimoles, micromoles, or nanomoles, 1000nM = 1 uM, 1000 uM = 1 mM) and lower numbers = tighter binding.

You can also look these numbers up at this place called the PDSP database, or look in the scientific literature for people publishing binding experiments.

 

[bunge]

Ah, I get it now I think.lol I thought affinity for a receptor was a guideline for how much activity will happen at that receptor. I think I understand it a little better now so many thanks for the clarification. I had read the wiki entries before but I couldnt glean all the info I was looking for.lol ive bookmarked the PDSP database so I can have a play with it later, so thanks again for your help. :-D