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a2 agonist (Clonidine) + a2 antagonist (Mianserin)

I

Ivanhoe

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Mar 16, 2004
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146
MIANSERINE
is an alpha-2 adrenergic receptor antagonist

CLONIDINE
is an alpha-2 adrenergic receptor agonist

What happens exactly in my brain when I take both medication?

->Do they act the exact opposite way, and each one cancel the action of the other?
->Do they have different ways of action on these same receptors?
 
You will feel the effects of the agonist*, but you'll need a higher dose in order for it to displace the antagonist. This also applies to the threashold dose of the agonist being raised, all in relation to the ammount of antagonist taken and time....etc.

To clarify, a receptor antagonist by definition is a chemical that simply blocks the receptor from ligands that would have activated it (in your case, both the agonist and endogenous epinephrine). An antagonist does not reduce the action of a receptor - for that you will need a "reverse agonist". Thats what I'm basing my logic on.

*Now, it gets a bit loopy from here, since the alpha receptor is an autoreceptor (think of it as a thermostat) - an agonist will actually reduce the effects of the adrenaline, making you actually feel less, subjectively. Think of it as a double-negative.

 
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An inverse agonist, not a reverse agonist.

It's complicated, because people assume that the alpha2 antagonist and hence serotonin increasing action of mianserin is how it is antidepressant, but it also effects other receptors, specifically 5-HT2 receptors, where it quite a bit more potent, as well as pretty much all other 5-HT receptors...

But yes, a concentration of clonidine high enough to have an effect should block a lot of the mianserin's actions.

Think of it like, the mianserin sits in the receptor and does do anything, while the clonidine sits in the receptor and activates it. In there are no other chemicals that will effect the receptor, a chemical like mianserin will have no effect, only when other chemicals, like noradrenaline or clonidine are around will it make things change, and that's by blocking their effect.
 
Mianserin is a really strong Histamine1 receptor antaonist, and a strong 5HT2a antagonist, and a 5HT2c inverse agonist (makes your dopamine neurons fire alot faster), and a good alpha2 antagonist, and a mild NARI and DARI, and other stuff. Mianserin also hits your opiate receptors a bit, and is synergistic with other opiates. I use this at the end of the night to go to sleep after speed or methadone. Completely relaxes my mind - much better than smoking cones to get to sleep. I personally hate THC on speed or opiates.

Clonidine is a strong alpha2 agonist, and a mild 5HT1a partial agonist, so your seratonin will go down a bit, and your noradrealine alot. It also does something with imildzine (spell?) receptors, to massively lower blood presure.

Just out of curiousity, Why would you take both together ?
 
You're really taking chances, fucking around with your blood pressure when you start playing around with alpha-2 agonists. Clonidine causes postural hypotension & mianserin is implicated in the same sort of thing. You might find you stand up & white out if you piss around with them (esp in conjunction with opiates)
 
fastandbulbous is right again, clonidine + opiates is a very risky combo due to the risk of hypotension. Save the clonidine for when you run out of opiates, it works wonders.

I have been curious ever since I was first prescribed clonidine a month ago (since it was the only thing my doc was willing to give me for sleep) about whether it is likely to make depression more severe... I know for a fact it makes it harder (not impossible) to have an erection... Also, I've read some reports of its withdrawal syndrome being unpleasant.

BTW, interesting factoid: Yohimbine is an a2 antagonist!
 
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