GBR 13069 dihydrochloride is a selective dopamine uptake inhibitor (IC50=40~51nM). GBR 13069 dihydrochloride increases the concentrations of dopamine and norepinephrine in the synaptic cleft by blocking the dopamine transporter (DAT) and norepinephrine transporter (NET), thereby modulating the physiological functions of neural circuits[1-2]. GBR 13069 dihydrochloride can be used for neuroscience research and pharmacological studies in models of dopamine-related neuropsychiatric disorders[3-4].
In vivo, GBR 13069 dihydrochloride (2µM) was co-injected with 6-hydroxydopamine (6-OHDA; 800µM) into the substantia nigra pars compacta (SNpc; 1µl) of rats. GBR 13069 dihydrochloride completely inhibited the 6-OHDA-induced degeneration of nigral dopaminergic neurons and the elevation of intracellular hydrogen peroxide (H2O2) levels in the SNpc[5]. GBR 13069 dihydrochloride (10mg/kg; i.p.) was administered to male white Swiss CD1 mice. GBR 13069 dihydrochloride occupied striatal dopamine uptake sites and significantly increased locomotor activity in the mice[6].
References:
[1] Heikkila RE, Manzino L. Behavioral properties of GBR 12909, GBR 13069 and GBR 13098: specific inhibitors of dopamine uptake. Eur J Pharmacol. 1984 Aug 17;103(3-4):241-8.
[2] Vaugeois JM, Bonnet JJ, Costentin J. In vivo labelling of the neuronal dopamine uptake complex in the mouse striatum by [3H]GBR 12783. Eur J Pharmacol. 1992 Jan 7;210(1):77-84.
[3] Sonsalla PK, Manzino L, Heikkila RE. Interactions of D1 and D2 dopamine receptors on the ipsilateral vs. contralateral side in rats with unilateral lesions of the dopaminergic nigrostriatal pathway. J Pharmacol Exp Ther. 1988 Oct;247(1):180-5.
[4] Sonsalla PK, Youngster SK, Kindt MV, et al. Characteristics of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine-induced neurotoxicity in the mouse. J Pharmacol Exp Ther. 1987 Sep;242(3):850-7.
[5] Nishio R, Morioka H, Takeuchi A, et al. Intracellular hydrogen peroxide produced by 6-hydroxydopamine is a trigger for nigral dopaminergic degeneration of rats via rapid influx of extracellular Zn2. Neurotoxicology. 2022 Mar;89:1-8.
[6] Vaugeois JM, Bonnet JJ, Duterte-Boucher D, et al. In vivo occupancy of the striatal dopamine uptake complex by various inhibitors does not predict their effects on locomotion. Eur J Pharmacol. 1993 Jan 12;230(2):195-201.
GBR 13069 dihydrochloride是一种具有选择性的多巴胺摄取抑制剂（IC50=40~51nM）。GBR 13069 dihydrochloride通过阻断多巴胺转运体（DAT）和去甲肾上腺素转运体（NET）来增加突触间隙中多巴胺和去甲肾上腺素的浓度，从而调节神经回路的生理功能[1-2]。GBR 13069 dihydrochloride可用于神经科学研究和多巴胺相关神经精神疾病模型的药理研究[3-4]。
在体内，将GBR 13069 dihydrochloride（2μM）与6-羟基多巴胺（6-OHDA；800μM）共同注射到大鼠的黑质致密部（SNpc；1μl）。GBR 13069 dihydrochloride完全抑制了由6-OHDA诱导的黑质多巴胺能神经变性和黑质细胞内过氧化氢（H2O2）水平升高[5]。GBR 13069 dihydrochloride（10mg/kg；腹腔注射）用于处理雄性白色Swiss CD1小鼠。GBR 13069 dihydrochloride能够占据纹状体多巴胺摄取位点并显著增加小鼠的运动活性[6]。