Understanding the Actions of Seroquel at Different Doses?

[DexyDevil]

I'm posting this in ADD because I feel my questions would best be answered here and I'd REALLY like some answers. So thanks you to any informed members who can help me.

I am prescribed 200mg of Seroquel in the evening. I also take Lyrica, Adderall, Remeron and Pristiq. I've been taking Seroquel for years for "Mood Disorder Not Otherwise Specified," whatever the hell that is supposed to mean. I understand that at certain doses Seroquel is merely a powerful antihistamine and that it becomes an antipsychotic at higher doses. If I'm correct, it antagonizes Serotonin at the dose I take, but DOES NOT antagonize Dopamine until you go above 300mg. At 400mg I get akathesia, which I get from most dopamine antagonists. Nothing under 400mg produces this effect.

Is my 200mg dose actually a mood stabilizer? Or is it merely a strong antihistamine that knocks me out every night? Am I getting any antipsychotic effect? And if so, by what mechanism of action?

If I am getting an antipsychotic effect, is it having any effect during the day? I don't notice much effect once I get up and get going. Am I just taking a glorified sleeping pill? Why do doctors prescribe Seroquel for mood disorders in a single instant release dose in the evening?

Also, if Seroquel is not much of an antipsychotic at doses below 300mg, is there any point to Seroquel XR which comes in a maximum of 400mg tablets? Wouldn't a slow release of even 400mg prevent Seroquel XR from ever reaching antipsychotic doses?

 

[sekio]

From Wikipedia, apparently quetiapine is a 5ht2a/2c antagonist at low doses. This would be responsible for a good potion of the e.g. antipsychotic, "trip-blocking", and appetite stimulant effects. It's also a histamine antagonist.

At higher doses it becomes a dopamine receptor antagonist, this is where akathisia comes from. It's hard to say exactly where the dose is that blocks dopamine, because it will vary in different people.

The affinity for histamine receptors (basicaly amount needed to block a receptor) is ~4nM, for 5ht2a receptors ~40nM, for dopamine D2 receptors around 400nM. So hypothetically, you might need ~5mg to be an effective antihistamine, ~50mg to start being an effective antipsychotics, and ~500mg to be an antidopaminergic.

Seroquel itself has a less sedating metabolite that has a long half life (12 hours). Since Seroquel is sedating, it's prescribed to be taken at night, and at least some of the dose will remain active as a maetabolite the next day. With continued daily dosing the levels will build up too.

 

[DexyDevil]

From Wikipedia, apparently quetiapine is a 5ht2a/2c antagonist at low doses. This would be responsible for a good potion of the e.g. antipsychotic, "trip-blocking", and appetite stimulant effects. It's also a histamine antagonist.

At higher doses it becomes a dopamine receptor antagonist, this is where akathisia comes from. It's hard to say exactly where the dose is that blocks dopamine, because it will vary in different people.

The affinity for histamine receptors (basicaly amount needed to block a receptor) is ~4nM, for 5ht2a receptors ~40nM, for dopamine D2 receptors around 400nM. So hypothetically, you might need ~5mg to be an effective antihistamine, ~50mg to start being an effective antipsychotics, and ~500mg to be an antidopaminergic.

Seroquel itself has a less sedating metabolite that has a long half life (12 hours). Since Seroquel is sedating, it's prescribed to be taken at night, and at least some of the dose will remain active as a maetabolite the next day. With continued daily dosing the levels will build up too.

Well done sir! That gives me all the answers I needed. Thanks.

 

[weekend addiction]

Someone posted a journal article on here not long ago that insisted Seroquel only acted as anti-histamine at 200 and under. I don't know enough about neuro-chemistry to confirm or deny his statements. Don't know where it is atm sorry.