Mirtazapine pharmacology: Opiate agonism and dopamine disinhibition

[Bucklecroft Rudy]

Mirtazapine is a fairly complex anti depressant as they go it has the following neural effects

Antinociception mediated by Kappa1,3 Delta and Mu opioid receptors
http://www.springerlink.com/content/2kx87825w7017h47/fulltext.pdf

Antagonism at 5ht 2abc,3,6,7
adrenergic receptor a1,2ac
H1
mAch

Inhibitor at norepinephrine transporter

Disinhibition of dopamine/norepinephrine in pleasure centres due to 5ht 2c antagonism


The above is highly highly interesting particularly the part concernig the downstream opiate activity. Kappa antagonism is known to antagonise mu agonism so they may simply cancel each other out. The increase in dopamine seems to run counter to my experience. I found that I was fairly depressed and experienced some anedhonia. I've also found mirtazapine to dull the effects of opiates almost entirely. What could cause these effects in light of the pharmacological profile of mirtazapine.

 

[negrogesic]

Don't have time for a proper response but it almost sounds as if you answered your own question here......

I take 120mg of the drug a day; while not subjectively opioidergic in a traditional sense, the degree of miosis may give the outward appearance of opioid abuse....

 

[ebola?]

Disinhibition of dopamine/norepinephrine in pleasure centres due to 5ht 2c antagonism

I think that people make too much of these downstream effects.

Kappa antagonism is known to antagonise mu agonism so they may simply cancel each other out.

Reference?

ebola

 

[BLreturn11]

mirtazapine - serious depersonalisation regardless (well in swimmers lets say) regardless of opioid agonist.

 

[Bucklecroft Rudy]

http://www.sciencedirect.com/science/article/pii/S0165614798011699

Im trying to find a reason why after I dosed the mirtazapine I literally was in almost constant withdrawal for a week unable to find relief since opiates werent doing anything. Kappa agonism could be responsible depending on how long the kappa effects persist. Enzymatic pathways could factor in as its a substrate for CYP2D6 and CYPP3A4. Then theres the adrenergic effects. But I feel like im missing something

 

[ebola?]

http://www.sciencedirect.com/science...65614798011699

This article argues that kappa-agonism antagonizes mu-effects downstream (with the argument that agonism at the two receptor-types involve distinct populations of cells), NOT that kappa-antagonism antagonizes mu-effects (as the OP argued).

well in swimmers lets say

Let's not.
1. We don't SWIM on here (it affords you no legal protection; it's annoying too).
2. You're afraid of someone finding out that you took mirtazapine??!

ebola

 

[Bucklecroft Rudy]

This article argues that kappa-agonism antagonizes mu-effects downstream (with the argument that agonism at the two receptor-types involve distinct populations of cells), NOT that kappa-antagonism antagonizes mu-effects (as the OP argued).



Let's not.
1. We don't SWIM on here (it affords you no legal protection; it's annoying too).
2. You're afraid of someone finding out that you took mirtazapine??!

ebola

"activation of the κ-receptor antagonizes various μ-receptor-mediated actions in the brain, including analgesia, tolerance, reward and memory processes. The neural mechanism for this potentially ubiquitous μ-opposing function of the κ-receptor is believed to involve distinct locations of the two opioid receptors on physiologically different cell types in local neuronal networks that are implicated in an opioid action."

This is the part I refer to - it sounds like any kappa agonism will result in inhibition of mu agonism. Perhaps not antagonism, but inhibition of the downstream effects of mu activation.

 

[paranoid android]

All mirtazapine seemed to do to me was make me eat half the stuff in the fridge before i passed out. I wouldn't compare it to opiates much as it feels like a strong anti-histamine that makes you super hungry. I took it while on oxycodone and morphine and i seemed to feel abit more drowsy but that happens with any sedating medication.

 

[Bucklecroft Rudy]

Im not comparing mirtazapine to opiates at all lol - im trying to establish the mechanism by which mu receptor activity is inhibited by mirtazapine