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Re: Upping Seroquel questions... SLS

Posted by desolationrower on May 4, 2011, at 0:09:30

In reply to Re: Upping Seroquel questions..., posted by SLS on May 3, 2011, at 22:54:21

> > that dosage of seroquel probably isn't doing much, other than helping put you to sleep. So i don't think it is directly causing a problem, but the underlying problem isn't really being dealt with on that regimine.
> >
> > Also, seroquel and its metabolite function as alpha2 antagonists, like mirtazapine.
>
> I wasn't aware of that.
>
> The active metabolite of Seroquel (quetiapine) is a potent NE reuptake inhibitor. (N-desalkylquetiapine / norquetiapine) It also is a partial agonist of 5-HT1a receptors.
>
> http://www.ncbi.nlm.nih.gov/pubmed/18059438
>
>
> - Scott

hm, i looked it up again and i think i was wrong in this conclusion. The affinity for a2 is similar to DA receptors, but probably not relevant at low doses. Both NET and a2 could be relevant at high doses. There are other reasons its not a great idea for adhd, but alpha2 is proabably not the biggest issue.

-d/r

here is the binding affinity
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=41375#section-15.2

here is a study on the levels of quietiapine vs metabolite

Quetiapine and Norquetiapine in Plasma and Cerebrospinal Fluid of Schizophrenic Patients Treated With Quetiapine: Correlations to Clinical Outcome and HVA, 5-HIAA, and MHPG in CSF
Abstract

This study investigated concentrations of quetiapine and norquetiapine in plasma and cerebrospinal fluid (CSF) in 22 schizophrenic patients after 4-week treatment with quetiapine (600 mg/d), which was preceded by a 3-week washout period. Blood and CSF samples were obtained on days 1 and 28, and CSF levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were measured at baseline and after 4 weeks of quetiapine, allowing calculations of differences in HVA (&#916;HVA), 5-HIAA (&#916;5-HIAA), and MHPG (&#916;MHPG) concentrations. Patients were assessed clinically, using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale at baseline and then at weekly intervals. Plasma levels of quetiapine and norquetiapine were 1110 608 and 444 226 ng/mL, and the corresponding CSF levels were 29 18 and 5 2 ng/mL, respectively. After the treatment, the levels of HVA, 5-HIAA, and MHPG were increased by 33%, 35%, and 33%, respectively (P < 0.001). A negative correlation was found between the decrease in PANSS positive subscale scores and CSF &#916;HVA (rrho = &#8722;0.690, P < 0.01), and the decrease in PANSS negative subscale scores both with CSF &#916;5-HIAA (rrho = &#8722;0.619, P = 0.02) and &#916;MHPG (rrho = &#8722;0.484, P = 0.038). Because, unfortunately, schizophrenic patients experience relapses even with the best available treatments, monitoring of CSF drug and metabolite levels might prove to be useful in tailoring individually adjusted treatments.


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poster:desolationrower thread:984447
URL: http://www.dr-bob.org/babble/20110502/msgs/984499.html