Selective serotonin reuptake inhibitor escitalopram inhibits 5-HT₃ receptor currents in NCB-20 cells
10.4196/kjpp.2019.23.6.509
- Author:
Yong Soo PARK
1
;
Ki Wug SUNG
Author Information
1. Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
- Publication Type:Original Article
- Keywords:
Depression;
Escitalopram;
Patch clamp;
Selective serotonin reuptake inhibitor;
5-hydroxytriptamine₃ receptor
- MeSH:
Antidepressive Agents;
Anxiety Disorders;
Citalopram;
Depression;
Methods;
Neuroblastoma;
Serotonin
- From:The Korean Journal of Physiology and Pharmacology
2019;23(6):509-517
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-HT₃) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through 5-HT₃ receptors. Using a whole-cell voltage clamp method, we recorded currents of 5-HT₃ receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express 5-HT₃ receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. EC50 of 5-HT on 5-HT₃ 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-HT₃ receptor channel with accelerating receptor desensitization. Although escitalopram accelerated 5-HT₃ receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit 5-HT₃ receptor currents in a non-competitive manner with the mechanism of open channel blocking.
