Haloperidol, a typical antipsychotic, inhibits 5-HT3 receptor-mediated currents in NCB-20 cells: a whole-cell patch-clamp study
Year: 2024
Type: article
Abstract: Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2).However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR.In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT) 3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells.When co-applied with 5-HT, haloperidol inhibited 5-HT 3 receptormediated currents in a concentration-dependent manner.A reduction in maximal effect (E max ) and an increase in EC 50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT 3 receptors.Haloperidol inhibited the activation of 5-HT 3 receptor, while also accelerating their deactivation and desensitization.The inhibitory effect of haloperidol showed no significant difference between pre-and co-application.Haloperidol did not alter the reversal potential of 5-HT 3 receptor currents.Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT 3 receptors.It did not show a use-dependent inhibition either.These findings suggest that haloperidol can exert its inhibitory effect on 5-HT 3 receptors by allosterically preventing opening of ion channels.This mechanistic insight enhances our understanding of relationships between 5-HT 3 receptors and pharmacological actions of antipsychotics.
DOI: 10.4196/kjpp.24.320
Authors: Yong Soo Park, Gyu Min Kim, Ho Jun Sung, Ju Yeong Yu, Ki-Wug Sung
Institution: Catholic University of Korea
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
Award: G919482796
OpenAlex ID: W4404578740