Posted by tom2228 on July 3, 2010, at 12:16:08
In reply to Re: MAOI + trileptal/ tegretol -- anybody?!, posted by ed_uk2010 on July 3, 2010, at 7:59:14
Thanks SLS, I saw that abstract before and referred my doc to it when we were discussing the safety of the combo.. Ya I originally thought the whole "structurally related to tricyclics" thing was a BS contraindication. But I did further research to be sure, and it turns out the risk of serotonin syndrome is not completely unfounded ... oxcarbazepine IS serotonergic (along with carbamazepine, you can find that on pub med also). Releasing agent to be specific, and I can definitely "feel" the serotonin -- I've been on 19 meds, I'm pretty sure I know what 5-HT feels like!
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http://www.ncbi.nlm.nih.gov/pubmed/16139430
Hippocampal dopamine and serotonin elevations as pharmacodynamic markers for the anticonvulsant efficacy of oxcarbazepine and 10,11-dihydro-10-hydroxycarbamazepine.
Abstract
We recently showed that dopamine (DA) and serotonin (5-HT) exert anticonvulsant effects against limbic seizures in rats mediated by hippocampal D(2) and 5-HT(1A) receptor stimulation. For exogenously administered monoamines, anticonvulsant activity was only observed following 70--400% and 80--350% increases in baseline levels for dopamine and serotonin, respectively. The aim of the present microdialysis study was to investigate whether oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxycarbamazepine (MHD) promote the release of hippocampal monoamines. Initially, concentration-response experiments were performed. Different concentrations of both compounds were perfused into the hippocampus via the microdialysis probe and tested for their effects on extracellular monoamine levels and anticonvulsant properties against pilocarpine-evoked seizures in rats. Anticonvulsant activity was always accompanied by significant increases in dopamine and serotonin levels. The anticonvulsant threshold concentrations for oxcarbazepine (100 microM) and 10,11-dihydro-10-hydroxycarbamazepine (250 microM) were associated with, respectively, 140 and 205% increases in hippocampal dopamine and 288 and 176% increases in serotonin concentrations. Co-perfusion of these anticonvulsant threshold concentrations for both compounds either with a selective D(2) or 5-HT(1A) antagonist abolished all anticonvulsant effects. This study shows that oxcarbazepine and 10,11-dihydro-10-hydroxycarbamazepine exert important monoamine promoting effects that, at least partly, contribute to the anticonvulsant mechanism of action of these compounds. The effects on dopamine and serotonin levels are therefore proposed as pharmacodynamic markers for the anticonvulsant activity of these compounds. These pharmacodynamic markers are here shown to be useful for the selection of anticonvulsant threshold concentrations of oxcarbazepine and 10,11-dihydro-10-hydroxycarbamazepine.
poster:tom2228
thread:951790
URL: http://www.dr-bob.org/babble/20100628/msgs/953121.html