Lamotrigine inhibits monoamine uptake in vitro and modulates 5-hydroxytryptamine uptake in rats

• Published in: European journal of pharmacology Vol. 358; no. 1; pp. 19 - 24
• Main Authors: Southam, Eric, Kirkby, Debbie, Higgins, Guy A., Hagan, Russell M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.09.1998; Elsevier
• Subjects: 5-HT (hydroxytryptamine, serotonin) uptake; Acetates - pharmacology; Amines; Animals; Anticonvulsant; Anticonvulsants - pharmacology; Biogenic Amines - antagonists & inhibitors; Biogenic Amines - pharmacokinetics; Biological and medical sciences; Bipolar disorder; Blood Platelets - drug effects; Blood Platelets - metabolism; Brain - drug effects; Brain - metabolism; Carbamazepine - pharmacology; Cyclohexanecarboxylic Acids; Dopamine - pharmacokinetics; Dopamine Uptake Inhibitors - pharmacology; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles - pharmacology; Lamotrigine; Lithium - pharmacology; Male; Medical sciences; Neuropharmacology; Norepinephrine - antagonists & inhibitors; Norepinephrine - pharmacokinetics; p-Chloroamphetamine - pharmacology; Pharmacology. Drug treatments; Phenytoin - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Serotonin - pharmacokinetics; Serotonin Agents - pharmacology; Serotonin Syndrome - prevention & control; Serotonin Uptake Inhibitors - pharmacology; Synaptosomes - drug effects; Synaptosomes - metabolism; Tetrodotoxin - pharmacology; Triazines - pharmacology; Valproic Acid - pharmacology; Zonisamide; Bipolar disorder; Anticonvulsant; Lamotrigine; 5-HT (hydroxytryptamine, serotonin) uptake; Human; Intraperitoneal administration; Rat; Serotonin; Psychotropic; Rodentia; Central nervous system; Reuptake inhibitor; In vitro; Uptake; In vivo; Vertebrata; Synaptosome; Platelet; Mammalia; Mood stabilizer; Animal; Mechanism of action; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00580-9

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 (IC 50s were 240 and 474 μM, respectively) by lamotrigine. Synaptosomal uptake of noradrenaline (IC 50 239 μM) and dopamine (IC 50 322 μM) 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.