RU 24969 is a widely used nonselective 5-HT1B/1A agonist with a Ki value of 0.38nM for the 5-HT1B receptor and 2.5nM for the 5-HT1A receptor, but with lower affinity for other receptor sites in the brain[1]. RU 24969 induces robust hyperlocomotor activity, characterized by increased forward locomotion and a concomitant reduction in fluid consumption[1].
In vitro, 10μM RU-24969 attenuated 21mM K⁺-induced [³H]-5-HT release in cultured rat frontal cortex slices, reducing it by approximately 30%[2].
In vivo, subcutaneous administration of RU 24969 at doses of 0.3, 1, and 3mg/kg produced a dose-dependent reduction in water intake in male SD rats within a 30-45min observation period. In addition, subcutaneous administration of RU 24969 (3mg/kg) significantly increased total forward locomotion within 15-45min after dosing[1]. Administration of RU-24969 at 10mg/kg by intraperitoneal injection decreased extracellular 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in rats[2].
References:
[1] Aronsen D, Webster J, Schenk S. RU 24969-produced adipsia and hyperlocomotion: differential role of 5HT 1A and 5HT 1B receptor mechanisms. Pharmacol Biochem Behav. 2014;124:1-4.
[2] Brazell MP, Marsden CA, Nisbet AP, Routledge C. The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo. Br J Pharmacol. 1985;86(1):209-216.
RU 24969是一种广泛使用的非选择性5-HT1B/1A激动剂，其对5-HT1B受体的Ki值为0.38nM，对5-HT1A受体的Ki值为2.5nM，而对大脑中的其他受体位点亲和力较低[1]。RU 24969可显著诱导过度运动，同时表现为向前运动增加及液体摄入减少[1]。
体外实验中，10μM RU-24969可显著抑制21mM K⁺诱导的培养大鼠额叶皮质切片中[³H]-5-HT的释放，抑制幅度约为30%[2]。
体内实验中，皮下注射0.3、1和3mg/kg剂量的RU 24969，在30-45分钟的观察时间内雄性SD大鼠的饮水量呈剂量依赖性降低。皮下注射3mg/kg RU 24969可在15-45分钟内显著提高大鼠总向前运动水平[1]。腹腔注射10mg/kg的RU-24969可显著降低大鼠细胞外5-HT及其代谢产物5-羟基吲哚乙酸（5-HIAA）的水平[2]。