Lamotrigine, an antiepileptic drug, inhibits 5-HT₃receptor currents in NCB-20 neuroblastoma cells

Abstract

Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)3 receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC50 value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, 5-HT3-mediated currents evoked by 1 mM dopamine, a partial 5-HT3 receptor agonist, were inhibited by lamotrigine co-application. The EC50 of 5-HT for 5-HT3 receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate 5-HT3 receptor desensitization, inhibited 5-HT3 receptor currents in a concentration-dependent manner. The deactivation of 5-HT3 receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of 5-HT3 receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the 5-HT3 receptor currents. These results indicate that lamotrigine inhibits 5-HT3-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.

Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells

“…Using equation (1), the calculated EC 50 of peak currents by 5-HT was 1.73±0.08 µM with a Hill coefficient of 2.44±0.08 (n=10). The shape of current trace, EC 50 , and Hill coefficient values are all similar with our previous investigations [ 22 23 ]. The currents induced by the application of 5-HT in NCB-20 cells were known to be mediated by the 5-HT 3 receptor activation, because these currents were completely blocked by the GR 38032F and IC 205-930, the potent 5-HT 3 receptor antagonists [ 24 ].…”

Slow on the Uptake, Progression to Heartbreak

“…Lamotrigine is a known mild 5-HT 3 receptor inhibitor, and the reported "labile mood" might have been a mild presentation of serotonin syndrome that was unrecognized. 7 The severity of the serotonin syndrome in our patient is likely caused by a combination of cocaine use and the exposure to higher than prescribed doses of lamotrigine. To our knowledge, our present case is the second reported case of serotonin syndrome associated with lamotrigine in combination with cocaine use.…”

Selective serotonin reuptake inhibitor escitalopram inhibits 5-HT3 receptor currents in NCB-20 cells

“…NCB-20 neuroblastoma cells provided by Dr. Lovinger (National Institute on Alcohol Abuse and Alcoholism, USA) have already been revealed to show 5-HT-induced current mediated by 5-HT 3 receptor, making it possible to test drug effect on 5-HT 3 receptor [28293031]. They were incubated in culture flasks filled with culture medium consisting of 89% Dulbecco Modified Eagle's Medium, 10% fetal bovine serum, and 1% hypoxanthine aminopterin thymidine supplement.…”