SB 699551, a biphenylmethylamine derivative, is a potent and selective 5-HT5A receptor antagonist [1]. SB 699551 can inhibit the activity of the androgen receptor (AR), reduce the mRNA and protein levels of PSA, and downregulate the expression of the AR target gene FKBP5[2]. SB 699551 has been widely used to regulate the hypotensive state in mouse models[3].
In vitro, SB 699551 significantly inhibits the formation of cell spheroids in HCC1954 cells and MCF-7 cells within 72 hours, with IC50 values of 0.3μM and 0.2μM, respectively[4]. Treatment with 3μM SB 699551 for 24 hours resulted in a significant decrease in the cell viability of AMO1 sgRNA-CT cells[5].
In vivo, subcutaneous injection of a single dose of SB 699551 (0.3mg/kg) prevented forgetting and amnesia in rats[6]. Intrathecal injection of 10μl at a concentration of 10nmol/rat for 10 minutes can reduce the analgesic effect induced by serotonin in rats[7]. A single intraperitoneal injection of SB 699551 (3mg/kg) within 2 hours improved the cognitive impairment induced by ketamine and enhanced the cognitive flexibility of rats[8].
References:
[1] Corbett D F, Heightman T D, Moss S F, et al. Discovery of a potent and selective 5-ht5A receptor antagonist by high-throughput chemistry[J]. Bioorganic & medicinal chemistry letters, 2005, 15(18): 4014-4018.
[2] Itsumi M, Shiota M, Sekino Y, et al. High‐throughput screen identifies 5‐HT receptor as a modulator of AR and a therapeutic target for prostate cancer[J]. The Prostate, 2020, 80(11): 885-894.
[3] Sánchez-Maldonado C, López-Sánchez P, Anguiano-Robledo L, et al. GR-127935-sensitive Mechanism Mediating Hypotension in Anesthetized Rats: Are 5-HT: 5B: Receptors Involved?[J]. Journal of Cardiovascular Pharmacology, 2015, 65(4): 335-341.
[4] Gwynne W D, Shakeel M S, Girgis-Gabardo A, et al. Antagonists of the serotonin receptor 5A target human breast tumor initiating cells[J]. BMC cancer, 2020, 20(1): 724.
[5] Du T, Song Y, Ray A, et al. Ubiquitin receptor PSMD4/Rpn10 is a novel therapeutic target in multiple myeloma[J]. Blood, The Journal of the American Society of Hematology, 2023, 141(21): 2599-2614.
[6] Aparicio-Nava L, Márquez-García L A, Meneses A. Effects of 5-HT5A receptor blockade on amnesia or forgetting[J]. Behavioural Brain Research, 2019, 357: 98-103.
[7] Muñoz-Islas E, Vidal-Cantú G C, Bravo-Hernández M, et al. Spinal 5-HT5A receptors mediate 5-HT-induced antinociception in several pain models in rats[J]. Pharmacology Biochemistry and Behavior, 2014, 120: 25-32.
[8] Nikiforuk A, Hołuj M, Kos T, et al. The effects of a 5-HT5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia[J]. Neuropharmacology, 2016, 105: 351-360.
SB 699551是一种联苯甲胺衍生物，为一种强效且选择性的5-HT5A受体拮抗剂[1]。SB 699551可抑制雄激素受体(AR)的活性，降低PSA的mRNA和蛋白水平，并下调AR靶基因FKBP5的表达[2]。SB 699551已广泛用于调控小鼠模型中的低血压状态[3]。
在体外，SB 699551在72小时内显著抑制了HCC1954细胞和MCF-7细胞中细胞球体的形成，IC50值分别为0.3μM和0.2μM[4]。用3μM的SB 699551处理24小时导致AMO1 sgRNA-CT细胞的细胞活力显著下降[6]。
在体内，单次皮下注射SB 699551（0.3mg/kg）可防止大鼠的遗忘和记忆缺失[6]。鞘内注射10μl浓度为10nmol/只的SB 699551 10分钟可降低5-羟色胺诱导的大鼠镇痛作用[7]。2小时内单次腹腔注射SB 699551（3mg/kg）改善了氯胺酮诱导的认知障碍并增强了大鼠的认知灵活性[8]。