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Re: Parnate trial SLS

Posted by desolationrower on August 25, 2008, at 20:36:06

In reply to Re: Parnate trial desolationrower, posted by SLS on August 25, 2008, at 9:04:11

yes, this study shows lower d2 occupancy:

D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study*1


Objective: Quetiapine is a novel antipsychotic agent with many atypical features, including low D2 and higher 5HT2A affinity in vitro, low propensity to induce extra-pyramidal side effects and minimal effects on prolactin levels. The purpose of this study was to investigate, using positron emission tomography (PET), the relationship between plasma concentrations of different doses of quetiapine and occupancy of D2 and 5HT2A receptors in schizophrenic patients. Methods: Five patients were treated with quetiapine (titrated to 750 or 450 mg/day) for 28 days, subsequently reduced weekly in a descending-dose schedule. Dopamine D2 and 5HT2A occupancies were determined using [11C] raclopride and [11C] N-methylspiperone as ligands, respectively, and PET imaging. 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. Quetiapine induced a consistently higher degree of 5HT2A receptor occupancy, with mean occupancies of 74 and 57% at doses of 750 and 450 mg/day, respectively. No EPS emerged during the trial and most of the pre-trial EPS resolved during the study. Conclusions: In clinically effective doses, quetiapine induced low occupancy at D2 receptors, which is consistent with atypical antipsychotics such as clozapine, and probably explains the lack of EPS observed in this trial. Correlations between receptor occupancy and plasma concentrations of quetiapine could not be calculated, although receptor occupancy increased with higher plasma concentrations for the 450 and 750 mg doses.

I also have in my notes k values of 160 & 220 for d2 & 5ht2a. Thats the smallest differential of antypicals other than aripiprazole.
Still, that isn't that much of a differential compared to other atypicals (other than aripiprazole). That is a higher dose too. If you want the 5ht2a antagonism for sleep quality, 25mg isn't going to get that.




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