Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9921138 | European Journal of Pharmacology | 2005 | 9 Pages |
Abstract
In vitro, lamotrigine inhibited rat brain MAO activities with Ki values (MAO-A, 15 μM; MAO-B, 18 μM) potentially within the therapeutic range for this drug. The effects of lamotrigine on the MAO-A activities of rat brain and human liver preparations were almost identical suggesting minimal species or tissue variation. In contrast, there was no (MAO-A) or minimal (MAO-B) reduction in brain MAO activities when assayed ex vivo following the administration of lamotrigine to rats. In vivo brain microdialysis failed to detect meaningful alterations in extracellular hippocampal or frontal cortex monoamine concentrations. Furthermore, lamotrigine did not modulate oral tyramine-induced hypertension in rats or 5-hydroxytryptophan-induced head shaking in mice, providing strong evidence that the drug does not perturb monoamine metabolism in vivo. The absence of observable effects of lamotrigine on monoamine disposition in vivo may be explained by the competitive and highly reversible nature of the interaction of lamotrigine with MAO isoforms. Thus, altered monoamine metabolism in vivo is unlikely to account for the antidepressant action of the drug in bipolar depression.
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Authors
Eric Southam, Rui Pereira, Sharon C. Stratton, Rebecca Sargent, Alison J. Ford, Lindsay J. Butterfield, Jane D. Wheable, Simon R.G. Beckett, Clare Roe, Charles A. Marsden, Russell M. Hagan,