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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by chess on June 7, 2005, at 10:09:13
anyone know what this means ...
"plasma elimination half-life of quetiapine with the occupancy half-lives at dopamine D2 and serotonin 5-HT2 receptors. The ratio of D2 : 5-HT2 receptor occupancy was 1:2, which is similar to that seen with clozapine. The results showed that while the plasma half-life was 5.3 h, the D2-receptor occupancy declined more slowly (half-life, 6 - 6.4 h) and serotonin 5-HT2 occupancy fell even more slowly (half-life, 20 - 27 h)"
does that mean that a single dose of Seroquel antagonizes 5-HT2 receptors for up to 20-27 hours? and thus that Seroquel can be taken once-a-day for anxiety?
Posted by PM80 on June 7, 2005, at 10:31:49
In reply to Seroquel Pharmacology question, posted by chess on June 7, 2005, at 10:09:13
I am not all that familiar with medical terminology, but I would read that the same way.
Also this has been true in my actual experience; I take Seroquel once a day (300mg at night) and it helps significantly with my excited symptoms all day. Excited symptoms for me are some typical hypomanic symptoms (racing thoughts, rapid speech, etc) and panic attacks. I would say that this drug can definitely chill people out, whether for bipolar manic/hypomanic symptoms or anxiety symptoms. Its only draw-back is that some people get negative side-effects.
Posted by ed_uk on June 7, 2005, at 11:43:58
In reply to Seroquel Pharmacology question, posted by chess on June 7, 2005, at 10:09:13
Hi Chess,
>serotonin 5-HT2 occupancy fell even more slowly (half-life, 20 - 27 h)
Occupancy (and therefore antagonism) of 5-HT2 receptors dropped by half after 20-27 hours.
>D2-receptor occupancy declined more slowly (half-life, 6 - 6.4 h)
It's action at D2 receptors may also be important for its anxiolytic effects.
>.......and thus that Seroquel can be taken once-a-day for anxiety?
It might be effective once daily- you'll have to try it and see!
Are you concerned that you might forget to take it if you had to take it more than once daily?
Kind regards,
Ed.
Posted by chess on June 7, 2005, at 14:33:22
In reply to Re: Seroquel Pharmacology question » chess, posted by ed_uk on June 7, 2005, at 11:43:58
how can its effect last for up to 20 hours if its half-life is only 6 hours?
> Hi Chess,
>
> >serotonin 5-HT2 occupancy fell even more slowly (half-life, 20 - 27 h)
>
> Occupancy (and therefore antagonism) of 5-HT2 receptors dropped by half after 20-27 hours.
>
> >D2-receptor occupancy declined more slowly (half-life, 6 - 6.4 h)
>
> It's action at D2 receptors may also be important for its anxiolytic effects.
>
> >.......and thus that Seroquel can be taken once-a-day for anxiety?
>
> It might be effective once daily- you'll have to try it and see!
>
> Are you concerned that you might forget to take it if you had to take it more than once daily?
>
> Kind regards,
> Ed.
Posted by ed_uk on June 7, 2005, at 15:00:54
In reply to Re: Seroquel Pharmacology question » ed_uk, posted by chess on June 7, 2005, at 14:33:22
LOL, you didn't answer my question:
Are you concerned that you might forget to take it if you had to take it more than once daily?
>how can its effect last for up to 20 hours if its half-life is only 6 hours?
Because it is still bound to receptors after 20 hours, even though very little remains in the blood. The half-life refers to the level of drug in the blood.
Regards,
Ed.
Posted by ed_uk on June 7, 2005, at 15:08:00
In reply to Re: Seroquel Pharmacology question » chess, posted by ed_uk on June 7, 2005, at 15:00:54
>The half-life refers to the level of drug in the blood.
Sorry, I didn't explain that properly. Here is a definition of half-life that I stole from a website.....
The period of time required for the concentration (eg. in the blood) or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount.
Ed.
Posted by chess on June 7, 2005, at 15:26:47
In reply to Re: Seroquel Pharmacology question » ed_uk, posted by ed_uk on June 7, 2005, at 15:08:00
so seroquel's half-life is 6 hours, and it lifespan is 12 hours, but its effect (occupancy) on serotonin 5-HT2 receptors is 40-54 hours (half-life occupancy being 20 - 27 h)
so that means that seroquel's half-life of 6 hours doesn't mean that it only works for 6 hours, right?
is it that some seroquel molecules BIND to 5HT-2 recepetors for 40-54 hours (half-life occupancy being 20 - 27 h) while other seroquel molecules that don't bind and stay free in the bloodstream are metabolized out of the body by 12 hours?
or maybe that seroquel makes some kind of effect to 5HT-2 receptors that lasts longer than the drug itself lasts in the body (kind of how taking one aspirin in the morning keeps platelets from sticking to each other all day even though aspirin's half-life is only 4 hours)?
Posted by SLS on June 7, 2005, at 16:13:50
In reply to Re: Seroquel Pharmacology question » ed_uk, posted by chess on June 7, 2005, at 14:33:22
Hi Chess.
How have you been?
> how can its effect last for up to 20 hours if its half-life is only 6 hours?
Although I think you are right in the case of Seroquel, it doesn't always follow that the biological activity of a drug is determined by its half-life. For instance, Parnate has a half-life of approximately 2 hours. Yet, its biological activity persists for days. Because it binds irreversibly to its target, its biological activity becomes more dependent on the body's ability to replace the target than to the removal of the drug from the blood stream.
With Seroquel, the drug does not bind very tightly to the dopamine receptor. In fact, it is the "weakest" of the atypical antipsychotics. It is constantly jumping on and off the receptor. My guess is that its activity is most dependent on the levels of drug in the blood stream, assuming that no other factors impede its exit from tissues. I imagine this is why Seroquel can make such an excellent sleep medication at dosages of 25-50mg. Come morning, most of the Seroquel is gone, and the person is able to start their day without too much residual sedation.
- Scott
Posted by chess on June 7, 2005, at 20:52:01
In reply to Re: Seroquel Pharmacology question, posted by SLS on June 7, 2005, at 16:13:50
Hi SLS
i'm hanging in there
how are you?re: seroquel
that's why i asked about its binding to 5HT-2 receptors, antagonizing these receptors is supposed to calm a person down, SSRIs down-regulate 5HT-2 receptors after a month while seroquel directly antagonizes them on first usei guess my main question is whether seroquel can be taken once-a-day for anxiety since its antagonization of 5HT-2 receptors persists for more than 24 hours based on the study i found (unless someone has different info)
> Hi Chess.
>
> How have you been?
>
> > how can its effect last for up to 20 hours if its half-life is only 6 hours?
>
> Although I think you are right in the case of Seroquel, it doesn't always follow that the biological activity of a drug is determined by its half-life. For instance, Parnate has a half-life of approximately 2 hours. Yet, its biological activity persists for days. Because it binds irreversibly to its target, its biological activity becomes more dependent on the body's ability to replace the target than to the removal of the drug from the blood stream.
>
> With Seroquel, the drug does not bind very tightly to the dopamine receptor. In fact, it is the "weakest" of the atypical antipsychotics. It is constantly jumping on and off the receptor. My guess is that its activity is most dependent on the levels of drug in the blood stream, assuming that no other factors impede its exit from tissues. I imagine this is why Seroquel can make such an excellent sleep medication at dosages of 25-50mg. Come morning, most of the Seroquel is gone, and the person is able to start their day without too much residual sedation.
>
>
> - Scott
Posted by SLS on June 8, 2005, at 6:07:17
In reply to Re: Seroquel Pharmacology question » SLS, posted by chess on June 7, 2005, at 20:52:01
> Hi SLS
> i'm hanging in there
> how are you?I'm actually beginning to benefit from Trileptal! I should probably redact the exclamation mark, as I have been teased before by drugs that start working and then stop within a week. I do feel slightly better, though.
> re: seroquel
> that's why i asked about its binding to 5HT-2 receptors, antagonizing these receptors is supposed to calm a person down, SSRIs down-regulate 5HT-2 receptors after a month while seroquel directly antagonizes them on first use
> i guess my main question is whether seroquel can be taken once-a-day for anxiety since its antagonization of 5HT-2 receptors persists for more than 24 hours based on the study i found (unless someone has different info)I didn't know that.
If I remember correctly, my doctor had me take Seroquel once a day (h.s.) at dosages over 100mg in the hopes it would exert an antidepressant effect. All it really did was to make me somewhat dysphoric and irritable.
I recently read two studies that suggested Seroquel possesses significant antidepressant properties; perhaps more than Zyprexa or Clozaril.
Because of its relatively short half-life, you would think that Cymbalta would have to be dosed twice a day. But those people whom respond best to it seem to need it only once a day.
Friggin' drugs...
- Scott
Posted by Cairo on June 8, 2005, at 19:09:46
In reply to Re: Seroquel Pharmacology question » SLS, posted by chess on June 7, 2005, at 20:52:01
I once used low dose Risperdal to sucessfully combat a Fibromyalgia flare. The advice I received was to use it low dose, and don't take more than a couple of weeks. It was very effective at 0.125mg, but made symptoms worse at higher doses. If you down regulate the 5HT-2 receptors too much, do they become overly sensitive? Is that why the advice to use only a couple of weeks? I can't tolerate SSRIs at all, but was surprised that Risperdal worked that first time. A second trial some months later didn't seem to work on the flare. Why?
I'm very interested in this as we may be augmenting Zoloft with Seroquel for my daughter's social phobia. She has similar FMS-like symptoms and I want to understand the what and hows of using Seroquel as the pdoc doesn't even want to to use it and doesn't seem to know much about this type of use, but may give it a trial based on the recommendation of a doctor at UPa we saw.
What about dopamine receptors with Seroquel?
Cairo
>... SSRIs down-regulate 5HT-2 receptors after a month while seroquel directly antagonizes them on first use
>
This is the end of the thread.
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