Mianserin

[iggy131313]

This is the first time in a study I have seen it said tyhat Mianserin blocks (is an antagonist) of 5ht1a

http://www.sciencedirect.com/science/ar ... 4694900337

If we could find more info aout this, then it would explain why long term use can cause complete recovery...

We need to start doing this methodically, if anyone can find studys about Mianserins effect at 5ht1a, lets post them here.....we also need a deeper understanding of what impace the alpha blocking both pre and post synaptically would do...from here we can enter into a joint study and see if our hypothisis proves correct...ghost what do you know about each property of mianserin? and what long term effect it would have?

[iull1k]

To what kind of adaptive changes can lead chronic receptor antagonism? (months,years). I searched but not found any concret information about this.

[iggy131313]

Im sorry Luke, I dont understand the question...could you rephrase

an antagonist with cause UPREGULATION

an agonist will cause DOWNREGULATION

thats the general rule, as you took a drug that caused severe downregulation of 5ht1a a drug tyat causes upregulation through antagonist would upregulate..is that what you mean?

there are exceptions to that rule, 5ht2a for example, can downregulate to both and agonist and antagonist..but 5ht1a doesnt work in that way (functional selectivity)

[iull1k]

But if we talk about 5ht2c?

[iggy131313]

5ht2c also acts via functional selectivity

its a little complex to explain it all right now, but mianserin is a DOWNREGULATING antagonist at 5ht2c which is great..as it works via functional selectivity, not all antagonists cause downregulation at 5ht2c some will cause upreg, some no change, but mianserin downregulates whilst still antagonising.....this would be instant, so if we look at the vidence I do not belive it is this mechanism that caused the lasting cure in the guy who recoved after 4 months on the drug...this is for 2 main reasons

1 - the cure would have been instant, the antagonism is within an hour, and the downregulation within 24 hours - it took 4 months for the guy who recovered to start to improve from pssd

2 - the receptors would have rebound and upregulated once the drug was removed, the guy who recoered has been off the drug for a year and still cured

so although 5ht2c antagonism disinhibits dopamine, its 5ht1a that pssd is mediated by...dopamine in the pre frontal cortex.....

[EricCartmanRJ]

amitryptiline blocks 5ht2c

[Ghost]

Also take into account that we need to up-regulate the presynaptic somatodentritic autorecepters, and not the postsynaptic receptors in the cortex and the hypothalamus. But studies I've seen show that agonists specifically downregulate presynaptic, so I'm assuming that antagonist would do opposite. That's what my textbooks would say at least. The only missing link is a study that shows this. I've been looking for one for months. It makes sense...right?

Zinc is a 5ht1a antagonist.

[Tenyears27]

I'm ocd tonight. Found a chemical, which im assuming is responsible for curing the guy, who's story I posted in 'general'

http://link.springer.com/article/10.1007%2FBF01244702

Whatever all that means?? Sounds important?

[iggy131313]

Hi ghost, yeah I think any antagonist/agonist that works on 5ht1a would effect both pre and post, same receptor differet location, but its pt luck as to where you get that upreg

thats why some get cured with st johns wort, some take longer than others etc etc

zinc has been working for people, that guy found that if he took zinc picolate at high doses, it made him feel worse, then he stopped and recovered, but it was transient, i think highers doses for longer might cause a more permenant upreg

[DoIt]

I'm taking zinc picolate that's maybe why I've seen some improvement? :/
I'm taking 30mg of zinc daily,, should I up it?