Sulpiride

Sulpiride is a novel, orally active dopamine D2/D3 receptor antagonist, classified as a benzamide atypical antipsychotic drug^[1-2]. Sulpiride is primarily used in the treatment of schizophrenia. Sulpiride exerts its effects by selectively blocking dopamine D2 receptors in the mesolimbic system, with minimal impact on other neurotransmitter receptors, resulting in lower anticholinergic side effects^[3-4].

In vitro, when mouse LMCAT fibroblasts were treated with Sulpiride (1-10μM) in combination with lipopolysaccharide (LPS; 1μg/mL) for 2 days, Sulpiride (5 and 10μM), Sulpiride significantly enhanced the inhibitory effect of LPS on corticosterone-induced chloramphenicol acetyltransferase (CAT) activity, aggravating the suppression of glucocorticoid receptor (GR) function under immune-activated conditions^[5]. In human ARPE-19 retinal pigment epithelial cells treated with Sulpiride (14μg/mL) for 24 hours, Sulpiride significantly upregulated the mRNA and protein expression levels of DRD1 and TGF-β2, while inhibiting the transcriptional and translational activity of DRD2, YAP, and TEAD^[6].

In vivo, in rats treated with Sulpiride (20, 40, or 100mg/kg via intraperitoneal injection) and observed from 5 to 20 minutes post-injection, Sulpiride rapidly modulated sensorimotor integration behavior by blocking D2 receptors, increasing the latency of head-turning movements induced by acoustic stimulation^[7]. In 4T1 breast cancer xenograft mice treated orally with a combination of Sulpiride (50mg/kg/day) and dexamethasone (8mg/kg/day) for 2 weeks, Sulpiride significantly inhibited tumor growth and lung metastasis, reduced MMP-2 expression, and increased E-cadherin levels^[8].

References:
[1] Caley CF, Weber SS. Sulpiride: an antipsychotic with selective dopaminergic antagonist properties. Ann Pharmacother. 1995 Feb;29(2):152-60.
[2] Bai M, Ma Z, Sun D, et al. Multiple drug transporters mediate the placental transport of sulpiride. Arch Toxicol. 2017 Dec;91(12):3873-3884.
[3] Costa E, Chen Y, Dong E, et al. GABAergic promoter hypermethylation as a model to study the neurochemistry of schizophrenia vulnerability. Expert Rev Neurother. 2009 Jan;9(1):87-98.
[4] Wang J, Sampson S. Sulpiride versus placebo for schizophrenia. Cochrane Database Syst Rev. 2014 Apr 11;2014(4):CD007811.
[5] Basta-Kaim A, Budziszewska B, Jaworska-Feil L, et al. Opposite effects of clozapine and sulpiride on the lipopolysaccharide-induced inhibition of the GR-mediated gene transcription in fibroblast cells. Pol J Pharmacol. 2003 Nov-Dec;55(6):1153-8.
[6] Fan J, Zhang Q, Zheng L, et al. Effect of dopamine on TGF-β2 secretion by human retinal pigment epithelial cells and the underlying mechanism. PLoS One. 2025 Nov 4;20(11):e0335526.
[7] Crescimanno G, Mannino M, Casarrubea M, et al. Effects of sulpiride on the orienting movement evoked By acoustic stimulation in the Rat. Pharmacol Biochem Behav. 2000 Aug;66(4):747-50.
[8] Li J, Yao QY, Xue JS, et al. Dopamine D2 receptor antagonist sulpiride enhances dexamethasone responses in the treatment of drug-resistant and metastatic breast cancer. Acta Pharmacol Sin. 2017 Sep;38(9):1282-1296.

Sulpiride是一种新型的、具有口服活性的多巴胺D2/D3受体拮抗剂，属于苯甲酰胺类非典型抗精神病药物^[1-2]。Sulpiride主要被用于治疗精神分裂症，Sulpiride通过选择性阻断中脑边缘系统的多巴胺D2受体发挥其作用，对其他神经递质受体影响较小，因此抗胆碱能副作用较轻^[3-4]。

在体外，Sulpiride（1-10μM）与脂多糖（LPS；1μg/mL）联合处理小鼠LMCAT成纤维细胞2天，Sulpiride（5和10μM）显著增强LPS对皮质酮诱导的氯霉素乙酰转移酶（CAT）活性的抑制作用，加剧了免疫激活条件下的GR功能抑制^[5]。Sulpiride（14μg/mL）处理人源ARPE-19视网膜色素上皮细胞24小时，Sulpiride显著上调DRD1和TGF-β2的mRNA及蛋白表达水平，并抑制DRD2、YAP和TEAD的转录与翻译活性^[6]。

在体内，Sulpiride（20、40、100mg/kg腹腔注射）处理大鼠（从注射后5分钟开始观察至20分钟），Sulpiride通过阻断D2受体快速调节感觉运动整合行为，增加由声刺激诱导的头部转向运动的潜伏期^[7]。Sulpiride（50mg/kg/day）联合地塞米松（8mg/kg/day）口服处理4T1转移性乳腺癌异种移植小鼠（治疗2周），Sulpiride显著抑制肿瘤生长和肺转移，降低MMP-2表达并增加E-钙黏蛋白水平^[8]。