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which serotonin receptors are involved in anxiety

Love that theyre advertising it as a potent antagonist of 5-ht3 receptors yet according to the sources they cite it doesnt even bind to the receptor.
 
Cotcha Yankinov said:
Those side effects are 5-HT1A activation related, and are apparently the reason why 5-HT1A full agonists haven't made it to market even though they may otherwise be helpful for some conditions.

With regards to Zyprexa's efficacy for your anxiety, this could be due to any number of reasons. Have you tried other antipsychotics that achieve appreciable dopamine receptor blockade, e.g. Risperidone? I wouldn't count Seroquel/quetiapine unless you've been up to very high doses, and even then its still different from other antipsychotics. The anti-dopamine properties can occasionally be helpful for some issues in particular people, such as intrusive thoughts/OCD/anxiety.
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would the dizzy stuff have gone away had I taken it for longer ? took it maybe 1 week. And wouldnt 5ht1a activation decrease serotonin?

It says buspar is an agonist on presynaptic 5ht1 receptors... so not the synapse 5ht1a receptor which if there is a lot serotonin matter since thats were serotonin receptors get activated? and it says on wiki its an agonist on postsynaptic 5-HT1A receptors.. so both pre and post synaptic activation but not in the synapse? When I say in the synapse I mean like the middel dont know whats it called I think its synapse? or synaptic cleft or somth.,

Does anyone know if Vortioxetine or viibryd increases 5ht1a activation in the SYNAPSE so it decreases serotonin receptors activation.
 
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trainman04 said:
It says buspar is an agonist on presynaptic 5ht1 receptors... so not the synapse 5ht1a receptor which if there is a lot serotonin matter since thats were serotonin receptors get activated? and it says on wiki its an agonist on postsynaptic 5-HT1A receptors.. so both pre and post synaptic activation but not in the synapse? When I say in the synapse I mean like the middel dont know whats it called I think its synapse? or synaptic cleft or somth.,

Does anyone know if Vortioxetine or viibryd increases 5ht1a activation in the SYNAPSE so it decreases serotonin receptors activation.
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I think you're misunderstanding the concept of a "synapse".
A synapse is where an electric signal gets transmitted across a gap by having a "pre-synaptic" cell release neurotransmitters which activate receptors on the "post-synaptic" cell across the gap, which then causes the signal to be propagated electrically again.

So a synapse can be compared to a national border - people either live this "this side of the border" or "across the border", but not "on the border".

Anyway, so you might be wondering: if the "pre-synaptic" cell releases neurotransmitters that bind to receptors on the "post-synaptic" side, then why are there also "pre-synaptic" receptors? Well, the cell needs to be able to know when it can stop dumping neurotransmitters into the synapse. Since some antipsychotic drugs (which are usually antagonists) will more readily bind to these pre-synaptic receptors, they can effectively "blind" the cell to the fact it has already released the target amount of neurotransmitters; employed at relatively low doses (i.e. before the dose gets high enough to significantly affect post-synaptic receptors), these antipsychotics can thus exert a stimulating/antidepressant effect rather than the sedating/anti-psychotic/anxiolytic effect you'd get from a full dose.
 
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On a sidenote, what the hell is up with BL no longer recognizing non-English punctuation marks?
 
doxylamine said:
Agonism at 5-HT1A and antagonism at 5-HT2 (notably 2A) receptors induces anxiolysis. I don't know much about 5-HT6 but I would assume antagonism would tend towards promoting anxiolysis more so than agonism would at this receptor. 5-HT3 agonists are anxiogenic, and with a lot of antidepressants and antipsychotics acting as antagonists this receptor it would seem that it indeed plays a part in their anxiolytic effects.

Edit: Quick look around determined that it is actually agonism, not antagonism, that may induce anxiolytic effects when it comes to the 5-HT6 receptor.
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Question though on this. 5HT3 receptors are located on GABA interneurons. Antagonism of the 5HT3 receptors in PET scans of vortioxetine-treated patients showed that even at 5mg were it is only a 5HT3 antagonist + SRI this reduced GABA firing and increased the release of glutamate (as well as virtually all of the other neurotransmitters including acetylcholine and histamine). I would theorize that for some people this could make anxiety worse and would explain why a lot of people with anxious depression don't do well on vortioxetine. Would also possibly be a hint as to why duloxetine beat vortioxetine as an active comparator in GAD trials.
 
IIRC you take a2 antagonists - a2 are also expressed post-synaptically on pyramidal cells in cortex as an example. Autoreceptors such as 5-HT1A are expressed on the soma as well, so autoreceptor expression certainly isn't limited to the terminal.
 
browri said:
Question though on this. 5HT3 receptors are located on GABA interneurons. Antagonism of the 5HT3 receptors in PET scans of vortioxetine-treated patients showed that even at 5mg were it is only a 5HT3 antagonist + SRI this reduced GABA firing and increased the release of glutamate (as well as virtually all of the other neurotransmitters including acetylcholine and histamine). I would theorize that for some people this could make anxiety worse and would explain why a lot of people with anxious depression don't do well on vortioxetine
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IIRC the predominant expression of 5-HT3 in hippocampus is on interneurons (no expression on principal cells I believe), and more active hippocampi may help combat some mental illnesses better. So in that sense, decreased 5-HT3/decreased GABA may actually be helpful to some, with regards to the hippocampi.

Serotonin can inhibit GABA interneurons via effects on 5-HT2 receptors as well.
 
Well I meant synaptic receptors rather than extrasynaptic ones, but yeah. I do. I take a mixture of clonidine for overload suppression,
And tizanidine as a muscle relaxer, that actually helps with the spasticity caused by the nerve damage to my leg.

And I seem to take very well to such noradrenergic release supression.
 
Cotcha Yankinov said:
IIRC the predominant expression of 5-HT3 in hippocampus is on interneurons (no expression on principal cells I believe), and more active hippocampi may help combat some mental illnesses better. So in that sense, decreased 5-HT3/decreased GABA may actually be helpful to some, with regards to the hippocampi.

Serotonin can inhibit GABA interneurons via effects on 5-HT2 receptors as well.
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Ah so perhaps 5HT2A antagonism then may cancel out some of the effects of 5HT3 antagonism?

I have a more anxious depression myself, and despite the mixed bag when it comes to vortioxetine and anxiety, I always wondered why it never was an issue for me. However, I also take valproate which appears to inhibit the breakdown of GABA and increase its synthesis. This could compensate for the reduced GABA firing. Confusing though as valproate has been shown to induce glutamate release as well and subsequently activate NMDA receptors. Here's what I'm on now

divalproex sodium 1000mg
vortioxetine 20mg
brexpiprazole 0.25mg
lisdexamfetamine 40mg
 
Oh, and Cotcha, its alpha2 agonists I take. ANTagonists just make me downright ill and feel like I want to fucking die.
 
I'm not sure about autoreceptors expressed on the dendrite (by definition in order for it to be an autoreceptor it has to be responding homeostatically to its own neurotransmitter release), but I imagine with volume transmission some transmitter release from the soma/terminal can float over to its own dendrite.

The other thing is that its been shown that some neurons do actually have vesicle dependent release of transmitters at the dendrite, especially with serotonin, where dendritic release can be seemingly potent.

" I seem to take very well to such noradrenergic release supression"

Another thing to consider is that a2 are expressed pre-synaptically on many cell types, including 5-HT cells among many others. Who knows what a2 are doing in the spinal cord, they're known to be expressed on cholinergic neurons in the brain as well, they could be on dorsal root ganglion.
 
Well there is also fast transmission via connexon and pannexin gap-junction channels. And possibly some contribution via ephaptic coupling effects between nearby neurons is there not? although the ephaptic coupling effect isn't strong, it wouldn't surprise me if such an emergent phenomenon is not being wasted, since the body, and particularly the nervous system does seem to be such a complex, subtle and quite astonishing organ, in its efficiency.

As for the alpha2 agonism, with me, its basically I get a lot of overstimulation from unfiltered sensory input. On the one hand it means I see things, I see so much that people miss, the smallest noise or subtle change of odor, I'll pick up on it, even if its just something being moved on another floor of the house, or someone cooking food many rooms away, I'll hear the click-click-click of the electric spark ignition system of the gas oven. Its a LOT of data to process, and essentially, I lack the filtration system that most, neurotypical folk do, like other auties. And the result when essentially, it becomes too much to process, is a sort of psychic buffer overflow, and its very draining. And accompanied by a lot of physical overstimulation that feels, very much like too much sympathetic activity. We auties and aspies, Rett's girls etc. generally know it as overloading. Pretty much does what it says on the tin. And thus, we overload.

I find that taking clonidine helps slam the brakes on it. And also welcome the relaxation that it and the tizanidine I take for the nerve damage afflicting my leg brings. It IS something of a compromise though. In that it damps down the excess sensory noise, but my nerve-jacked senses aren't quite as acute and razor-sharp. The problem though with razor-edged senses, is that razors can have a tendency to cut one. Although my sensory perception is still probably better than most.

And also considering the ligands used, clonidine, tizandine, they are not only alpha2 adrenoreceptor agonists, they are imidazoline derivatives and as such, agonists at the various subtypes of imidazoline receptor binding sites. Still. The hypotensive effects aside, it is good to be rid of the damn overloading. And still, it does need some suppression for me to be at my best.
 
I have a question about receptors. Blocking 5ht2c increases dopamine / norepherpine in one part of the brain. Are there any other receptors in which when you block or agonize which increases those two neurontransmitters?
 
Limpet_Chicken said:
Well there is also fast transmission via connexon and pannexin gap-junction channels. And possibly some contribution via ephaptic coupling effects between nearby neurons is there not? although the ephaptic coupling effect isn't strong, it wouldn't surprise me if such an emergent phenomenon is not being wasted, since the body, and particularly the nervous system does seem to be such a complex, subtle and quite astonishing organ, in its efficiency.
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This reminds me that there are actually some electrical synapse autoreceptors, named autapses (some are also regular chemical synapses as well), whereby a neuron's axon projects back onto its own dendrites https://www.nature.com/articles/srep30914
 
trainman04 said:
I have a question about receptors. Blocking 5ht2c increases dopamine / norepherpine in one part of the brain. Are there any other receptors in which when you block or agonize which increases those two neurontransmitters?
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Since you were off on an "increasing NMDA receptor activation tangent", I'll throw out there that blocking NMDA receptors increases dopamine/norepinephrine.
 
Cotcha Yankinov said:
Since you were off on an "increasing NMDA receptor activation tangent", I'll throw out there that blocking NMDA receptors increases dopamine/norepinephrine.
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You just know that trainman04 is going to run off and try to score a prescription for medicinal PCP now :|
 
Cotcha Yankinov said:
Since you were off on an "increasing NMDA receptor activation tangent", I'll throw out there that blocking NMDA receptors increases dopamine/norepinephrine.
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hmm sounds like ur lying to stop me from trying NMDA. too bad im not smart enough to understand .
 
PCP, ketamine and other dissociatives are also dopamine D2 receptor agonists.
 
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