Selective serotonin reuptake inhibitor escitalopram inhibits 5-HT(3) receptor currents in NCB-20 cells

Escitalopram is one of selective serotonin reuptake inhibitor antidepressants. As an S-enantiomer of citalopram, it shows better therapeutic outcome in depression and anxiety disorder treatment because it has higher selectivity for serotonin reuptake transporter than citalopram. The objective of this study was to determine the direct inhibitory effect of escitalopram on 5-hydroxytryptamine type 3 (5-HT(3)) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through 5-HT(3) receptors. Using a whole-cell voltage clamp method, we recorded currents of 5-HT(3) receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express 5-HT(3) receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. EC(50) of 5-HT on 5-HT(3) receptor currents was increased by escitalopram while the maximal peak amplitude was reduced by escitalopram. The inhibitory effect of escitalopram was voltage independent. Escitalopram worked more effectively when it was co-applied with 5-HT than pre-application of escitalopram. Moreover, escitalopram showed fast association and dissociation to the open state of 5-HT(3) receptor channel with accelerating receptor desensitization. Although escitalopram accelerated 5-HT(3) receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit 5-HT(3) receptor currents in a non-competitive manner with the mechanism of open channel blocking.