SR 57227 hydrochloride is a potent serotonin type-3 (5-HT3) receptor agonist with the ability to cross the blood brain barrier [1]. SR 57227 hydrochloride can enhance the expression of c-Fos induced by fasting in the brainstem and hypothalamus of mice, and block the downregulation of proopiomelanocortin expression in the hypothalamus and tyrosine hydroxylase expression in the brain stem caused by fasting, thereby inhibiting the feeding behavior of mice[2]. SR 57227 hydrochloride is widely incorporated into the design of ionizable lipid to develop lipid nanoparticles (LNP) for systemic delivery of mRNA to the brain[3].
In vivo, SR 57227 hydrochloride treatment via intraperitoneal injection at a single dose (1mg/kg) for one hour can increase the locomotor activity of female mice and promote the vertical standing behaviors[4]. A single intraperitoneal injection of SR 57227 hydrochloride (10mg/kg) for 30 minutes reduced the pain-like behaviors in mice triggered by environmental cues[5]. Continuous intraperitoneal injection of SR 57227 hydrochloride (20mg/kg; twice a day) for 8 consecutive days significantly inhibited the death caused by spontaneous seizure in C57-DR mice[6]. A single intraperitoneal injection of SR 57227 hydrochloride (40mg/kg) at 30 minutes significantly reduced susceptibility to seizure-induced respiratory arrest (S-IRA) that leads to death in the DBA/1 mouse model of sudden unexpected death in epilepsy[7].
References:
[1] Bachy A, Héaulme M, Giudice A, et al. SR 57227A: a potent and selective agonist at central and peripheral 5-HT3 receptors in vitro and in vivo[J]. European journal of pharmacology, 1993, 237(2-3): 299-309.
[2] Li B, Shao D, Luo Y, et al. Role of 5-HT3 receptor on food intake in fed and fasted mice[J]. PLoS One, 2015, 10(3): e0121473.
[3] Cao D, Hou X, Wang C, et al. Lipid nanoparticles for mRNA delivery in brain via systemic administration[J]. Science Advances, 2025, 11(33): eadw0730.
[4] Brookshire B R, Jones S R. Direct and indirect 5-HT receptor agonists produce gender-specific effects on locomotor and vertical activities in C57 BL/6J mice[J]. Pharmacology Biochemistry and Behavior, 2009, 94(1): 194-203.
[5] Nakamura Y, Sumi T, Mitani O, et al. SR 57227A, a serotonin type-3 receptor agonist, as a candidate analgesic agent targeting nociplastic pain[J]. Biochemical and biophysical research communications, 2022, 622: 143-148.
[6] Guo J, Min D, Farrell E K, et al. Enhancing the action of serotonin by three different mechanisms prevents spontaneous seizure‐induced mortality in Dravet mice[J]. Epilepsia, 2024, 65(6): 1791-1800.
[7] Faingold C L, Randall M, Zeng C, et al. Serotonergic agents act on 5-HT3 receptors in the brain to block seizure-induced respiratory arrest in the DBA/1 mouse model of SUDEP[J]. Epilepsy & Behavior, 2016, 64: 166-170.
SR 57227 hydrochloride是一种强效的serotonin type-3 (5-HT3)受体激动剂，能够穿过血脑屏障[1]。SR 57227 hydrochloride可增强禁食诱导的小鼠脑干和下丘脑中c-Fos的表达，并阻断禁食引起的下丘脑proopiomelanocortin表达下调和脑干tyrosine hydroxylase表达下调，从而抑制小鼠的进食行为[2]。SR 57227 hydrochloride被广泛用于可电离脂质的设计中，以开发用于将mRNA 全身递送至大脑的脂质纳米颗粒[3]。
在体内，单次腹腔注射SR 57227 hydrochloride（1mg/kg）一小时，可增加雌性小鼠的运动活性，并促进垂直站立行为[4]。单次腹腔注射SR 57227 hydrochloride（10mg/kg）30分钟，可减少由环境线索触发的小鼠疼痛样行为[5]。连续8天每天两次腹腔注射SR 57227 hydrochloride（20mg/kg），可显著抑制C57-DR小鼠因自发性癫痫发作导致的死亡[6]。在DBA/1小鼠癫痫猝死模型中，单次腹腔注射SR 57227 hydrochloride（40mg/kg）30分钟，可显著降低导致死亡的癫痫诱发呼吸暂停(S-IRA)的易感性[7]。