Haloperidol, a typical antipsychotic, inhibits 5-HT₃ receptor-mediated currents in NCB-20 cells: a whole-cell patch-clamp study

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yong Soo Park Gyu Min Kim Ho Jun Sung Ju Yeong Yu Ki-Wug Sung
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제3호, 349~358쪽, 전체 10쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.05.01

국문 초록

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-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (Emax) and an increase in EC50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 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-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.

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키워드

Antipsychotics Haloperidol Patch clamp Schizophrenia 5-HT3 receptor