how r smaller doses more sedating than higher ones? and question about 2400mg of seroquel !

[swanny]

after reading a few posts on this website ppl keep saying that with seroquel that smaller doses such as 25mg will knock you out more than lets say 200mg. that doesnt make sense coz i always thought higher doses would knock you out more?? plz explain.

[DKnight]

after reading a few posts on this website ppl keep saying that with seroquel that smaller doses such as 25mg will knock you out more than lets say 200mg. that doesnt make sense coz i always thought higher doses would knock you out more?? plz explain.

I'm curious about this as well.

I want to know if 50mg seroquel is as sedating or more sedating than 300mg.

[AnneMarie]

This provides a pretty good description of how Seroquel works. http://thelastpsychiatrist.com/2007/07/the_most_important_article_on.html

[swanny]

This provides a pretty good description of how Seroquel works. http://thelastpsychi...article_on.html

fantastic link but i still dont get it! lol? how the heck is 500mg of seroquel not more sedating than 25mg? can someone plz explain it without giving a link plz plz plz

[swanny]

ive got a better question actually. is there a dose of seroquel that stops being more sedating? for example yes 50mg would knock you out but then if u increased it to 200 then 400. could the sedation stop getting worse once you get to 400. hypothetical only. just an example.

[tryp]

Hey,

Alright, let's try it this way. Your brain talks to itself using chemicals called neurotransmitters. They send their message by going from one part of the brain to another and binding to their receptor.

Seroquel, and other psych meds, work by changing this signal in various ways.

Seroquel changes the signals of a few different chemicals: one is histamine (which makes you sleepy), another is serotonin and another is dopamine. It changes their signals by binding to their receptors and either making the message more powerful or by weakening it.

Now, here's the complicated part. There is only a limited number of these receptors in your brain, and Seroquel doesn't like them all the same.

Imagine that the receptors are like pieces of candy, and each dose of Seroquel is like a hungry kid. Now, suppose you have 10 lollypops to represent histamine, 20 tootsie rolls to represent dopamine receptors, and 20 hershey's kisses to represent serotonin receptors.

Now, all these kids, since they're all Seroquel, have the same taste in candy. They all like lollypops a LOT, tootsie rolls a bunch too, and sort of hershey's kisses.

So you take 25 mg of Seroquel - that's like 1 kid. He likes lollypops best, so he eats one. That's like Seroquel at 25 mg going into your brain and going straight to amplify the histamine signal and make you sleepy. Now, suppose you take 50 mg. Another kid comes and goes straight for the lollypops. You get more sleepy. And so on and so forth.

But eventually, after 10 kids have come, around 300+ mg of Seroquel, there aren't any more lollypops. So you can take more seroquel/invite more kids, but there just aren't any more lollypops/histamine receptors for them to take. So even though they're running around eating the kisses and the tootsie rolls, no matter how much you take, or how many kids you invite, nothing else involving lollypops/sedation is going to happen because you've eaten them all/are out of receptors. Hence the constant level of sedation above like 300 mgs (and that's a ballpark and pretty individual for each person)

[bpladybug]

Hey,

Alright, let's try it this way. Your brain talks to itself using chemicals called neurotransmitters. They send their message by going from one part of the brain to another and binding to their receptor.

Seroquel, and other psych meds, work by changing this signal in various ways.

Seroquel changes the signals of a few different chemicals: one is histamine (which makes you sleepy), another is serotonin and another is dopamine. It changes their signals by binding to their receptors and either making the message more powerful or by weakening it.

Now, here's the complicated part. There is only a limited number of these receptors in your brain, and Seroquel doesn't like them all the same.

Imagine that the receptors are like pieces of candy, and each dose of Seroquel is like a hungry kid. Now, suppose you have 10 lollypops to represent histamine, 20 tootsie rolls to represent dopamine receptors, and 20 hershey's kisses to represent serotonin receptors.

Now, all these kids, since they're all Seroquel, have the same taste in candy. They all like lollypops a LOT, tootsie rolls a bunch too, and sort of hershey's kisses.

So you take 25 mg of Seroquel - that's like 1 kid. He likes lollypops best, so he eats one. That's like Seroquel at 25 mg going into your brain and going straight to amplify the histamine signal and make you sleepy. Now, suppose you take 50 mg. Another kid comes and goes straight for the lollypops. You get more sleepy. And so on and so forth.

But eventually, after 10 kids have come, around 300+ mg of Seroquel, there aren't any more lollypops. So you can take more seroquel/invite more kids, but there just aren't any more lollypops/histamine receptors for them to take. So even though they're running around eating the kisses and the tootsie rolls, no matter how much you take, or how many kids you invite, nothing else involving lollypops/sedation is going to happen because you've eaten them all/are out of receptors. Hence the constant level of sedation above like 300 mgs (and that's a ballpark and pretty individual for each person)

wow, I want an animated cartoon of this!! lol

[swanny]

thanks for all the replies. i just got another question. there is this guy on youtube that claimed he used to be on 2400mg of seroquel for schizo ! thats a lot! is there a certain dosage that if you go over wont make much difference to schizophrenia? if so how many milligrams is it?

[swanny]

this guy was on 2400mg http://www.youtube.com/watch?v=KwjiojvZXyI what do you think?

[nibblerd]

this guy was on 2400mg http://www.youtube.com/watch?v=KwjiojvZXyI what do you think?

I'd be questioning the motives of his well-respected psychiatrist for prescribing such a massive dose. I mean, there are certainly more potent AAPs that could have helped without those side effects, no?

As for the "therapeutic ceiling" for psychiatric meds, it all depends on the underlying cause or mechanism of the disorder. There is a limit to how many receptors, what type of receptors, and where it binds in the human body. There are numbers available somewhere on the receptor occupancy % of the various antipsychotics, but the one I remember off the top of my head is Abilify - 3mg can cover 70% of D2 receptors, and it goes up to 90% at doses around 30/40mg. If the drug does not cover everything at the highest saturation (with or without horrifying side effects) then the next thing is to try a different drug.

Unrelated: He mentions recreational use of Seroquel -- I've heard of someone snorting lithium when they could not obtain cocaine. Sounds... stupid.

[domovoi]

Unrelated: He mentions recreational use of Seroquel -- I've heard of someone snorting lithium when they could not obtain cocaine. Sounds... stupid.

are you serious???????? oh my god that's retarded.

about initial question: until about 25-200 mg seroquel works as an antihistamine. antihistamines make you sleep. 200-500 it is a dopamine antagonist. dopamine antagonists help with symptoms of schizophrenia, hence you're less sleepy at that dose. at 500-800 mg it modulates serotonin somehow. this theoretically helps with depression. seroquel is like 3 meds in one, depending on the dosages. that means its effects are different depending on the dosage. this includes somnolence.

[nibblerd]

Unrelated: He mentions recreational use of Seroquel -- I've heard of someone snorting lithium when they could not obtain cocaine. Sounds... stupid.

are you serious???????? oh my god that's retarded.

about initial question: until about 25-200 mg seroquel works as an antihistamine. antihistamines make you sleep. 200-500 it is a dopamine antagonist. dopamine antagonists help with symptoms of schizophrenia, hence you're less sleepy at that dose. at 500-800 mg it modulates serotonin somehow. this theoretically helps with depression. seroquel is like 3 meds in one, depending on the dosages. that means its effects are different depending on the dosage. this includes somnolence.

There is an "overflow" effect with some drugs, wherein new sites are occupied only after previous possibilities are saturated (if that makes sense). Take a large enough dose of some drugs and some really weird pharmacological shit can happen; 300mg of mirtazapine is intensely psychedelic because its activity as a 5-HT2a antagonist reverses direction and it becomes a partial agonist. I don't think any studies have been done on Seroquel in the 2000mg+ range?

I saw that quetiapine has moderate activity as a serotonin and nor-epinephrine reuptake inhibitor (SNRI) at higher doses. Well, that's that!

[AnneMarie]

Unrelated: He mentions recreational use of Seroquel -- I've heard of someone snorting lithium when they could not obtain cocaine. Sounds... stupid.

are you serious???????? oh my god that's retarded.

about initial question: until about 25-200 mg seroquel works as an antihistamine. antihistamines make you sleep. 200-500 it is a dopamine antagonist. dopamine antagonists help with symptoms of schizophrenia, hence you're less sleepy at that dose. at 500-800 mg it modulates serotonin somehow. this theoretically helps with depression. seroquel is like 3 meds in one, depending on the dosages. that means its effects are different depending on the dosage. this includes somnolence.

Seroquel is generally thought to act act as an antidepressant around 150mg to 300mg. Some may need higher. YMMV, but lower doses seem to be current thinking for depression.

[pineappleupside]

According to their prescribing info for BP depression, you have to be at 300mg..

[domovoi]

Unrelated: He mentions recreational use of Seroquel -- I've heard of someone snorting lithium when they could not obtain cocaine. Sounds... stupid.

are you serious???????? oh my god that's retarded.

about initial question: until about 25-200 mg seroquel works as an antihistamine. antihistamines make you sleep. 200-500 it is a dopamine antagonist. dopamine antagonists help with symptoms of schizophrenia, hence you're less sleepy at that dose. at 500-800 mg it modulates serotonin somehow. this theoretically helps with depression. seroquel is like 3 meds in one, depending on the dosages. that means its effects are different depending on the dosage. this includes somnolence.

Seroquel is generally thought to act act as an antidepressant around 150mg to 300mg. Some may need higher. YMMV, but lower doses seem to be current thinking for depression.

i'm sorry i got my stuff wrong! you guys are right

[Velvet Elvis]

[Pamito]

I was on 1600mg Seroquel at one time , and believe me, it didn't feel very 'recreational' lol. But it didn't feel any more sedating than 800mg. That was one thing that stood out. I also don't understand how 25 mg is more sedating than a higher dose, but this thread puts a few ideas out there. Histamine, eh?

[nibblerd]

I was on 1600mg Seroquel at one time , and believe me, it didn't feel very 'recreational' lol. But it didn't feel any more sedating than 800mg. That was one thing that stood out. I also don't understand how 25 mg is more sedating than a higher dose, but this thread puts a few ideas out there. Histamine, eh?

I bet that its action as an SNRI somehow boosts energy and counteracts the histamine sedation. Maybe?

[Velvet Elvis]

If my brain works tomorrow I'll try to correct all of you.

[nibblerd]

If my brain works tomorrow I'll try to correct all of you.

Thank you, O Great One.

[Aurochs]

Ok, it seems like everybody got close, but nobody hit the bullseye. Let's try again.

Let's clarify some things. First, quetiapine does not magically stop being an antihistamine at 200mg. You simply stop feeling any increase in the antihistamine effects, because the drug has already occupied most of the available H₁ receptors. Second, PET studies (like the one cited in Stacia's link) do not show that non-selective drugs suddenly increase binding to other receptors when the one they like most is unavailable. This is consistent with basic chemistry. Just like adding more of a chemical to a reaction increases the speed of the reaction (up to a point) by making particle collisions more likely, increasing the concentration of a drug just makes it more likely that it will bind to non-preferred receptors.

If you perceive a decrease in sedation, there could be two reasons for this. One is simple tolerance. Try taking 50mg of diphenhydramine before bed for a week. The first few days, you'll be out cold in 10 minutes. By the end of the week, you likely won't feel anything from it. Of course, quetiapine is not diphenhydramine, and tolerance to quetiapine doesn't seem to build that quickly. It certainly didn't for me. But I never got above 50mg/day, and higher doses may cause the brain to adjust faster.

The second possible mechanism of reduced sedation would be an increase in binding to other receptors. Quetiapine binds to a wide array of neurotransmitter receptors, some of which may counteract the sedation from H₁ antagonism. Off the top of my head, none of these are significant wakefulness promoters, though 5-HT_2A antagonism is known to improve sleep quality.

Now, nibblerd has once again posted a few really odd things without any sort of citation. Sigh.

Take a large enough dose of some drugs and some really weird pharmacological shit can happen; 300mg of mirtazapine is intensely psychedelic because its activity as a 5-HT2a antagonist reverses direction and it becomes a partial agonist.

Really? So, mirtazapine suddenly changes its composition when there's a lot of it? 5-HT_2A can change its properties in the presence of a lot of mirtazapine? Please provide evidence of these remarkable properties of mirtazapine and the 5-HT_2A receptor.

I saw that quetiapine has moderate activity as a serotonin and nor-epinephrine reuptake inhibitor (SNRI) at higher doses. [snip] I bet that its action as an SNRI somehow boosts energy and counteracts the histamine sedation. Maybe?

I'm not aware of any appreciable activity at any monoamine transporter on the part of quetiapine. N-desalkylquetiapine, which does have a lot of activity at the norepinephrine transporter, has an affinity of about 1,000 nM at the serotonin transporter (ref). Given that both quetiapine and its metabolite are alpha antagonists, I'm not sure how to interpret the norepinephrine reuptake inhibition.

And finally, having taken low-dose Seroquel before, I can understand how it might be abusable for some people. Having been in the hospital after taking low-dose Seroquel and high-dose gin at the same time, I can understand how it would be rather silly to abuse... anything.

[nibblerd]

Now, nibblerd has once again posted a few really odd things without any sort of citation. Sigh.

Take a large enough dose of some drugs and some really weird pharmacological shit can happen; 300mg of mirtazapine is intensely psychedelic because its activity as a 5-HT2a antagonist reverses direction and it becomes a partial agonist.

Really? So, mirtazapine suddenly changes its composition when there's a lot of it? 5-HT_2A can change its properties in the presence of a lot of mirtazapine? Please provide evidence of these remarkable properties of mirtazapine and the 5-HT_2A receptor.

I saw that quetiapine has moderate activity as a serotonin and nor-epinephrine reuptake inhibitor (SNRI) at higher doses. [snip] I bet that its action as an SNRI somehow boosts energy and counteracts the histamine sedation. Maybe?

I'm not aware of any appreciable activity at any monoamine transporter on the part of quetiapine. N-desalkylquetiapine, which does have a lot of activity at the norepinephrine transporter, has an affinity of about 1,000 nM at the serotonin transporter (ref). Given that both quetiapine and its metabolite are alpha antagonists, I'm not sure how to interpret the norepinephrine reuptake inhibition.

WRT mirtazapine:

I did not say that it changes its composition, but there is something about dosing to higher concentrations that changes the 5-HT2a effects. You can see that it has action on the acetylcholine system as well as the three major uptake pumps. It could be both a [weak] partial 5-HT2a agonist and antagonist, or something related to neurotransmitter uptake.

However, about Seroquel; I mistook information I saw on Ziprasidone which does have moderate SNRI properties, with Seroquel which does not. My bad.

[Aurochs]

WRT mirtazapine:

I did not say that it changes its composition, but there is something about dosing to higher concentrations that changes the 5-HT2a effects. You can see that it has action on the acetylcholine system as well as the three major uptake pumps. It could be both a [weak] partial 5-HT2a agonist and antagonist, or something related to neurotransmitter uptake.

Your figure shows that mirtazapine's affinity for "acetylcholine" receptors (miscarinic? nicotinic? it doesn't say, but I'll assume muscarinic) is ~1,000 nM, and well over 1,000 nM for the three monoamine transporters. That's hardly significant at recommended doses. Further, psychedelic effects can't be explained in terms of reuptake inhibition or muscarinic antagonism, unless you can demonstrate that every SSRI and most antipyschotics are psychedelics. Finally, you didn't actually provide a citation, you just posted some random mystery image. Yes, I can see its URL. No, that's not enough.

You'll also have to explain how mirtazapine is both an agonist and an antagonist at the same time. I'm aware that this is generally possible, but I don't believe it's been demonstrated for mirtazapine.

[deesnowboard]

Seroquel works differently at different doses. When first marketed, it was considered an antipsychotic med, but doctors were finding it worked well only at higher doses. Doctors also found it worked for depression at moderate doses, and caused sedation at really low doses. They found the side effect of sedation handy, as it causes better REM sleep (few meds do) and is not addictive. It has to do with which neurotransmitters are blocked at which dose (lower levels block seratonin from disintegrating in the brain, higher levels block norepinepherine) If you look up mechanisms of action on Seroquel, you can get more detailed info on how the drug works on the human body

[Cattitude]

I'm not going to delve into any major science here, I'm just going to tell you, from my experience, how Seroquel worked for me.

I have found that, as far as somnolence is concerned, I basically develop a tolerance for Seroquel once I've been on a dose for a while. But, once I get up to a certain dose, not only do I not feel as sleepy (if at all) when I've been on it for a while, I begin to get restless leg syndrome, which gets worse the higher the dose I take.

So - now I'm on only 100mg of Seroquel along with zopiclone for sleep. As far as I know, the pdoc hasn't prescribed Seroquel to me for any other purpose.

Re recreational use: I have heard of people who grind up the pills ('quel) and snort them either alone or mixed with cocaine. Doesn't make sense to me either.

[ProudMami135]

I really don't know why the lower dosages are more sedating, but I know it is definitely true! At one point, my doc had me taking 200mg of seroquel in the morning and 600 at night. I ended up skipping the 200 in the morning because it made me feel so "blah" and I didn't want to do anything but go back to bed.

Higher dosages can still be sedating, just not so much.

[chimpmaster]

FYI i was on 1600mg seroquel from memory - maybe 5 years ago now.

It worked reasonably well, except for the weight gain and zombie-itis.