Haloperidol is a classic antipsychotic and dopamine D2-like receptor antagonist, as well as an ion channel inhibitor that inhibits a variety of ion channels, such as G-protein-activated inwardly rectifying potassium channels, calcium-activated potassium channels, HERG and HEAG potassium channels, as well as L-, N- and P-type calcium channels[1-4].
Haloperidol (5-100 μM) treatment significantly decreased the viability of U87, U251, and T98 cells with IC50 values of 23, 38, and 35 μM, respectively. Haloperidol induced apoptosis of glioblastoma cells in a dose-dependent manner and inhibited cell migration and expression of CD24 and CD44[2]. Nontoxic concentrations of Haloperidol (1-30 μM) showed a dose-dependent enhancement of VBL cytotoxicity in VBL-resistant human leukemia (K562/VBL) cells, but had no similar effect in parent cells[3].
In adult male Sprague-Dawley rats, Haloperidol (0.05 and 2 mg/kg) had no effect on cell proliferation in the dentate gyrus (DG) and the number of surviving newly generated neurons in DG after bromodeoxyuracil (BrdU) administration[4]. In adult male Wistar rats treated with Haloperidol (1-10 mg/kg), levels of the thiobarbituric acid (TBA) active substance (TBAR) in the striatum (ST) were increased and TBAR levels in the cortex (CX) were decreased[5].
References:
[1] Yang S B, Proks P, Ashcroft F M, et al. Inhibition of ATP‐sensitive potassium channels by haloperidol[J]. British journal of pharmacology, 2004, 143(8): 960-967.
[2] Papadopoulos F, Isihou R, Alexiou G A, et al. Haloperidol induced cell cycle arrest and apoptosis in glioblastoma cells[J]. Biomedicines, 2020, 8(12): 595.
[3] Kataoka Y, Ishikawa M, Miura M, et al. Reversal of vinblastine resistance in human leukemic cells by haloperidol and dihydrohaloperidol[J]. Biological and Pharmaceutical Bulletin, 2001, 24(6): 612-617.
[4] Halim N D, Weickert C S, McClintock B W, et al. Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus[J]. Neuropsychopharmacology, 2004, 29(6): 1063-1069.
[5] Toru M, Takashima M. Haloperidol in large doses reduces the cataleptic response and increases noradrenaline metabolism in the brain of the rat[J]. Neuropharmacology, 1985, 24(3): 231-236.
Haloperidol是一种典型的抗精神病药和多巴胺D2样受体拮抗剂，也是离子通道抑制剂，可抑制多种离子通道，如G蛋白激活的内向整流钾通道、钙激活钾通道、HERG和HEAG钾通道以及L、N和P型钙通道[1-4]。
Haloperidol（5-100 μM）处理显著降低了U87、U251和T98细胞活力，IC50值分别为23、38和35 μM。Haloperidol以剂量依赖性方式诱导胶质母细胞瘤细胞凋亡，抑制细胞迁移和CD24、CD44的表达[2]。无毒浓度的Haloperidol（1-30 μM）在长春碱（VBL）耐药人白血病（K562/VBL）细胞中呈浓度依赖性增强VBL的细胞毒性，但在亲本细胞中没有类似作用[3]。
在成年雄性Sprague-Dawley大鼠中，Haloperidol（0.05和2 mg/kg）对齿状回（DG）中的细胞增殖及溴脱氧尿嘧啶（BrdU）给药后DG中存活的新生成神经元的数量没有影响[4]。在接受Haloperidol（1-10 mg/kg）治疗的成年雄性Wistar大鼠中，纹状体（ST）中的硫代巴比妥酸（TBA）活性物质（TBAR）水平增加，皮质（CX）中的TBAR水平降低[5]。