Seroquel/Quetiapine question

[kaiba]

http://en.wikipedia.org/wiki/Seroquel

http://thelastpsychiatrist.com/2007/07/the_most_important_article_on.html

http://thelastpsychiatrist.com/2007/08/arent_two_antipsychotics_bette.html

http://www.europeanneuropsychopharmacology.com/article/S0924-977X(00)00133-4/abstract

http://www.ncbi.nlm.nih.gov/pubmed/15029469?dopt=Abstract


According to the articles/journals above, Seroquel/Quetiapine "is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with clinically negligible anticholinergic properties." Furthermore, low dose Seroquel "acts primarily as a histamine receptor blocker (antihistamine)." In addition, "at high doses (over 250 mg) quetiapine starts blocking significant amounts of dopamine receptors."

My question is: Up to what dose is Seroquel no longer a histamine receptor blocker (antihistamine) and starts blocking other receptors such as serotonin and dopamine?

Please post references, articles, journals and your experiences.

 

[sekio]

From a cursory breakdown of the wikipedia IC50s.

IC50 dose relative to IC50 for H1
H1 = 1x
adrenergic a1 = 3x
adrenergic a2 = 9x
D2 = 11x
5-HT1A = 23.9x
D1 = 42.2x

 

[kaiba]

From a cursory breakdown of the wikipedia IC50s.

Thanks for the reply!

I understand how you got the multiples from wikipedia but I still don't get it.

So what would be the equivalent doses in mg/milligrams for each receptor?

H1 = 1x = X mg
adrenergic a1 = 3x = Y mg
adrenergic a2 = 9x = Z mg
D2 = 11x = A mg
5-HT1A = 23.9x = B mg
D1 = 42.2x = C mg

What would be the values/doses of X, Y, Z, A, B and C in milligrams/mg?

 

[sekio]

It is impossible to tell, it's dependent on the person's metabolism, weight, whether there's fat or not in the stomach, distribution through tissues and fluids of the drug, changes in receptor sensitivity and density etc.

Wikipedia says that doses above 200mg are significant dopamine blockers so I would imagine doses of 25-50mg are going to be primarily antihistamine/A1/A2 effects with little dopamine blockade. Serotonergic effects and whatnot probably come into play over 100mg for most people.

The thing to remember is that Seroquel will block all of these to some extent as long as it's present in the blood (An IC50 is the inhibitory concentraton for 50% of the receptors, it says nothing about the slope of the curve). It's just that there's usually not enough to produce a significant effect at low dosages.

 

[23536]

come on now, even 25 mg cancels stimulant and psychedelic psychosis. How can you say that there is not significant antipsychotic action even at low doses?

I think the H1 antagonism begins to manifest at doses lower than 25 mg. I've eaten half a 25 and have been sedated.

 

[23536]

So what would be the equivalent doses in mg/milligrams for each receptor?

H1 = 1x = X mg
adrenergic a1 = 3x = Y mg
adrenergic a2 = 9x = Z mg
D2 = 11x = A mg
5-HT1A = 23.9x = B mg
D1 = 42.2x = C mg

What would be the values/doses of X, Y, Z, A, B and C in milligrams/mg?

your problem has only one variable: mass of H1 antagonism dose. All other variables are multiples of that dose.

Take a protractor and a razor blade and slice a 25 mg Seroquel into eight equal slices. Eat one 3 mg slice. If no sedation is felt, eat 2 slices the following day. And so on. Proceed until you feel sedation.

 

[rangrz]

come on now, even 25 mg cancels stimulant and psychedelic psychosis. How can you say that there is not significant antipsychotic action even at low doses?

I think the H1 antagonism begins to manifest at doses lower than 25 mg. I've eaten half a 25 and have been sedated.

really? I can take 25mg after toking up on crystal and not notice anything; so I think its safe to say at 25mg the DA/NE/5HT block of little clinical significance.

Indeed, as per what it says, I notice me or my friends require around 200mg to start knocking down a hard stim, and in working as medic at raves, at least 100mg to have serious effect on psychedelics (admin'ed for a bad trip)

I don't know where'd you find a receptor binding vs dose curve, but the standard numbers do line up show pretty much what to expect in terms of clinical concern.

 

[Nagelfar]

I've seen people who've taken seroquel for dopesickness to sleep, and others find said person cannot drive but they don't know themselves that they're crawling on the floor with their eyes closed trying to find the door saying that they're fine; this is after being given some meth to try and wake them up.

 

[23536]

really? I can take 25mg after toking up on crystal and not notice anything; so I think its safe to say at 25mg the DA/NE/5HT block of little clinical significance.

Indeed, as per what it says, I notice me or my friends require around 200mg to start knocking down a hard stim, and in working as medic at raves, at least 100mg to have serious effect on psychedelics (admin'ed for a bad trip)

I guess it's dose and substance dependent. My experience with quetiapine as neuroleptic antidote comes from heavy crack smoking or Adderall ingestion and 25 mg has always sufficed.

 

[kaiba]

come on now, even 25 mg cancels stimulant and psychedelic psychosis. How can you say that there is not significant antipsychotic action even at low doses?

I think the H1 antagonism begins to manifest at doses lower than 25 mg. I've eaten half a 25 and have been sedated.

Seroquel at low doses is primarily an antihistamine - there is very little or no antipsychotic action. Sedation is a common side effect of antihistamines. Seroquel is a really/very strong antihistamine.

At very low doses quetiapine acts primarily as a histamine receptor blocker (antihistamine) and α1-adrenergic blocker.

http://en.wikipedia.org/wiki/Seroquel

Quetiapine is not classified as a controlled substance, "abusive self-administration seems to be driven by quetiapine’s sedative and anxiolytic effects (to help with sleep or to 'calm down') rather than by its antipsychotic properties."

http://en.wikipedia.org/wiki/Seroquel

Regarding antipsychotics/dopamine:

Results: Mean D2 receptor occupancies of 41 and 30% were observed at quetiapine doses of 750 and 450 mg/day. At lower dose levels no occupancy could be determined.

http://www.europeanneuropsychopharmacology.com/article/S0924-977X(00)00133-4/abstract

Regarding sedation/sleep:

Quetiapine 25 mg and 100 mg significantly improved sleep induction and continuity under standard and acoustic stress conditions. Increases in total sleep time, sleep efficiency, percentage sleep stage 2 and subjective sleep quality were seen.

http://www.ncbi.nlm.nih.gov/pubmed/15029469?dopt=Abstract

 

[kaiba]

Regarding Seroquel's antihistamine and/or antipsychotic (dopamine) action:

The mechanism of reinforcement for this misuse is unknown, but we hypothesize that it is related to quetiapine's pharmacological profile as an antihistamine with a relative low affinity for dopamine receptors.

http://www.sciencedirect.com/science/article/pii/S0149763409001699

 

[23536]

a lot of the research involving quetiapine is specious at best--if not altogether falsified by AstraZeneca. The company for years has been trying to push the drug as a one-size-fits-all psychiatric drug, and the clinical trials that they have financed utilize investigators and trial sites that are well known to the company and intentionally elicit a response over placebo.

I've worked for several psychiatrists who prescribe low-dose quetiapine for psychotic symptoms (MDD w/ psychotic features or BPD w/ psychotic features). I formerly (years ago) was on a regimen of 50 mg po qhs.

It's not entirely impossible that my psychotic crises resolved spontaneously, but the same would have to hold true for all the other patients whom I've encountered that have remained stable on low dose quetiapine.

 

[skillet]

I formerly (years ago) was on a regimen of 50 mg po qhs.

It's not entirely impossible that my psychotic crises resolved spontaneously, but the same would have to hold true for all the other patients whom I've encountered that have remained stable on low dose quetiapine.

What's the alternative, that seroquel cured you?!

 

[23536]

What's the alternative, that seroquel cured you?!

there's nothing magical about the drug; it's a major tranq. It treated the symptoms probably as well as pentobarbital would've treated them (good drug that one!)

 

[skillet]

Yeah I know, maybe I should have added a lol at the end to make it clearer :D

 

[hazed420]

Interesting read since i have a high tolerance to Seroquel and take 50mg per dose and that lasts me a good 6-8 hours, total dosage is 100mg per 24 hours.

My life was a dull place at 200mg a day.

I have and never had any problems driving even on the higher doses with xanax (all prescribed)

 

[kaiba]

I've worked for several psychiatrists who prescribe low-dose quetiapine for psychotic symptoms (MDD w/ psychotic features or BPD w/ psychotic features). I formerly (years ago) was on a regimen of 50 mg po qhs.

What does MDD and BPD mean? Is "qhs" 4 times per day? How long did you take Seroquel? Any side effects?

You felt sedated/sleepy when you took the 50 mg Seroquel, right?

 

[skillet]

MDD is manic depressive disorder, BPD is bipolar disorder, though I'm not sure what distinguishes the two...

q.h.s. = every bedtime (from Latin quaque hora somni) (wiki)

 

[23536]

sorry about that; MDD is major depressive disorder

...for like 6 months. It was less stupefying than olanzapine, but it still dulled my thought process and killed my originality & creativity (like hitting the mute button on the music of the skull, which is why I discontinued it as I was writing for a living back then).

 

[Jakeperson]

come on now, even 25 mg cancels stimulant and psychedelic psychosis. How can you say that there is not significant antipsychotic action even at low doses?

It didnt even touch DOI, 25mg did nothing, 100mg did nothing except mild sedation, 200mg did nothing more, 300mg gave me RLS with mild-moderate sedation (enough to stop me getting out of bed) It turned from a horrible trip to a horrible trip stuck in bed with RLS.