GR 113808 is a potent and selective 5-HT4 receptor antagonist with a pKb of 8.8[1]. GR 113808 can be used in the study of gastrointestinal motility disorders, neurological diseases and tumors[2, 3]. GR 113808 can attenuate morphine-stimulated dopamine release in the striatum of rats[4].
In vivo, GR 113808 (1mg/kg) treated with colitis mice by enema for 5-7 days reversed the significant improvement of Tegaserod on clinical and histological damage to the colon[5]. GR 113808 (16μg) treated with dorsal hippocampal (dHIP) injection in rats with medial forebrain bundle (MFB) lesions increased dopamine levels in the striatum, medial prefrontal cortex (mPFC), lateral habenula (LHb) and ventral hippocampus (vHIP), and increased serotonin (5-HT) levels in the LHb[6].
References:
[1] Kaumann A J. Blockade of human atrial 5-HT4 receptors by GR 113808[J]. British journal of pharmacology, 1993, 110(3): 1172.
[2] Kato S, Fujiwara I, Yoshida N. Nitrogen‐containing heteroalicycles with serotonin receptor binding affinity: Development of gastroprokinetic and antiemetic agents[J]. Medicinal research reviews, 1999, 19(1): 25-73.
[3] Guillemot J, Compagnon P, Cartier D, et al. Metoclopramide stimulates catecholamine-and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors[J]. Endocrine-Related Cancer, 2009, 16(1): 281.
[4] Pozzi L, Trabace L, Invernizzi R, et al. Intranigral GR-113808, a selective 5-HT4 receptor antagonist, attenuates morphine-stimulated dopamine release in the rat striatum[J]. Brain research, 1995, 692(1-2): 265-268.
[5] Spohn S N, Bianco F, Scott R B, et al. Protective actions of epithelial 5-hydroxytryptamine 4 receptors in normal and inflamed colon[J]. Gastroenterology, 2016, 151(5): 933-944. e3.
[6] Wang J W, Gao F, Wang Z L, et al. Activation and blockade of dorsal hippocampal serotonin4 receptors produce antidepressant effects in the hemiparkinsonian rats[J]. Brain Research, 2021, 1761: 147426.
GR 113808是一种有效和选择性的5-HT4受体拮抗剂，pKb=8.8[1]。GR 113808能够用于胃肠动力障碍、神经系统疾病及肿瘤研究[2, 3]。GR 113808能够减弱吗啡刺激的大鼠纹状体中多巴胺的释放[4]。
在体内，GR 113808（1mg/kg）通过灌肠治疗结肠炎小鼠5-7天，逆转了Tegaserod对结肠临床和组织学损伤的显著改善效果[5]。GR 113808（16μg）通过背侧海马体（dHIP）注射治疗内侧前脑束（MFB）病变大鼠，增加了纹状体、内侧前额皮质（mPFC）、外侧缰核（LHb）和腹侧海马（vHIP）中的多巴胺水平，并增加了LHb中的5-羟色胺（5-HT）水平[6]。