NGB 2904 is a potent, selective, orally active, and brain-penetrant antagonist of the dopamine D3 receptor, with a Ki of 1.4nM[1]. NGB 2904 targets the D3 receptor, blocking the addiction effect mediated by the D3 receptor and reducing the extracellular dopamine level[2]. NGB 2904 has been widely used in the study of dopamine neuron activity to regulate locomotion in rodents[3].
In vitro, NGB 2904 treatment for 72h inhibited the proliferation of H460 cells and H460 cells overexpressing ABCG2, with IC50 values of 70µM and 159µM, respectively[4]. 100nM NGB 2904 was pre-treated for 1 hour, which promoted the activation of glycolysis and the upregulation of glycolysis-related enzyme expression in synovial fibroblasts from patients with rheumatoid arthritis (RASFs) stimulated by 80µM dopamine (24 hours)[5].
In vivo, NGB 2904 treatment via intraperitoneal injection at a dose of 3mg/kg 20 minutes before the novel object recognition and open field tests improved recognition and spatial memory deficits in a mouse model of Alzheimer's disease without affecting locomotor activity or anxiety-related behaviors[6]. Intraperitoneal injection of NGB 2904 (1mg/kg) led to a decrease in the body weight of mice 24 hours later and the induction of depressive-like behaviors[7]. 30 minutes before the test, intraperitoneal injection of NGB 2904 inhibits cocaine cue-induced reinstatement of drug-seeking behavior in rats[8].
References:[1] Yuan J, Chen X, Brodbeck R, et al. NGB 2904 and NGB 2849: two highly selective dopamine D3 receptor antagonists[J]. Bioorganic & medicinal chemistry letters, 1998, 8(19): 2715-2718.
[2] Xi Z X, Gardner E L. Pharmacological actions of NGB 2904, a selective dopamine D3 receptor antagonist, in animal models of drug addiction[J]. CNS drug reviews, 2007, 13(2): 240-259.
[3] Pritchard L M, Newman A H, McNamara R K, et al. The dopamine D3 receptor antagonist NGB 2904 increases spontaneous and amphetamine-stimulated locomotion[J]. Pharmacology Biochemistry and Behavior, 2007, 86(4): 718-726.
[4] Hussein N, Amawi H, Karthikeyan C, et al. The dopamine D3 receptor antagonists PG01037, NGB2904, SB277011A, and U99194 reverse ABCG2 transporter-mediated drug resistance in cancer cell lines[J]. Cancer letters, 2017, 396: 167-180.
[5] Xue L, Xu S, Li M, et al. The dopamine D3 receptor regulates dopamine-induced activation and glycolytic metabolism of synovial fibroblasts in rheumatoid arthritis[J]. Clinical and Experimental Immunology, 2026, 220(1): uxag008.
[6] Tropea M R, Aceto G, Trovato R C, et al. Dopamine D3 receptor blockade restores hippocampal synaptic plasticity and rescues memory deficits in Alzheimer's disease mouse models[J]. Frontiers in Aging Neuroscience, 2026, 18: 1840697.
[7] Wang J, Jia Y, Li G, et al. The dopamine receptor D3 regulates lipopolysaccharide-induced depressive-like behavior in mice[J]. International Journal of Neuropsychopharmacology, 2018, 21(5): 448-460.
[8] Gilbert J G, Newman A H, Gardner E L, et al. Acute administration of SB‐277011A, NGB 2904, or BP 897 inhibits cocaine cue‐induced reinstatement of drug‐seeking behavior in rats: Role of dopamine D3 receptors[J]. Synapse, 2005, 57(1): 17-28.