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Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
Lamotrigine inhibits monoamine uptake in vitro and modulates 5-hydroxytryptamine uptake in rats
E Southam1, D Kirkby, G A Higgins
1Neuroscience Unit, Glaxo Wellcome Medicines Research Centre, Stevenage, Herts, UK. es36365@ggr.co.uk
Abstract:
Lamotrigine is a novel anticonvulsant drug which also stabilises mood in bipolar illness via an unknown mechanism. We report the concentration-dependent inhibition of 5-hydroxytryptamine (5-HT) uptake in both human platelets and rat brain synaptosomes (IC50s were 240 and 474 microM, respectively) by lamotrigine. Synaptosomal uptake of noradrenaline (IC50 239 microM) and dopamine (IC50 322 microM) was also inhibited. Tetrodotoxin failed to modulate 5-HT uptake suggesting that sodium channel blockade does not mediate the lamotrigine effect. Lithium, sodium valproate, zonisamide, and carbamazepine all possess anti-manic activity but only the latter inhibited 5-HT uptake. The inhibition of the p-chloroamphetamine-induced 5-HT syndrome in rats suggests that lamotrigine also inhibits 5-HT uptake in vivo. These effects probably reflect an affinity for biogenic amine transporters. However, at present, it remains uncertain whether, at clinically effective doses, these effects contribute significantly to the efficacy of lamotrigine in bipolar illness.
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