SSR 149415 is a selective, non-peptide antagonist of the Vasopressin V1b Receptor[1-2]. SSR 149415 is primarily used in research related to the treatment of stress-related disorders, such as depression and anxiety [3-4].
In vitro, pretreatment of In-R1-G9 cells with SSR 149415 (0.66–1.2nM) for 15 minutes, followed by stimulation with Arginine Vasopressin (AVP; 100nM) for 4–15 minutes, significantly inhibited AVP-induced intracellular calcium elevation and glucagon secretion, while also antagonized AVP-mediated cell proliferation[5].
In vivo, pretreatment of NMRI mice with SSR 149415 (10mg/kg) via intraperitoneal injection, followed by administration of AVP (20μg/kg), significantly reversed the anticonvulsant effect of AVP[7]. In a rat model of acute myocardial infarction (AMI), microinjection of SSR 149415 (40ng; 0.1μL) into the paraventricular nucleus (PVN) significantly ameliorated AMI-induced hemodynamic dysfunction and cardiac injury[8].
References:
[1] Serradeil-Le Gal C, Raufaste D, Derick S, et al. Biological characterization of rodent and human vasopressin V1b receptors using SSR-149415, a nonpeptide V1b receptor ligand. Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R938-49.
[2] Decaux G, Soupart A, Vassart G. Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet. 2008 May 10;371(9624):1624-32.
[3] Dannenhoffer CA, Kim EU, Saalfield J, et al. Oxytocin and vasopressin modulation of social anxiety following adolescent intermittent ethanol exposure. Psychopharmacology (Berl). 2018 Oct;235(10):3065-3077.
[4] Braida D, Donzelli A, Martucci R, et al. Neurohypophyseal hormones manipulation modulate social and anxiety-related behavior in zebrafish. Psychopharmacology (Berl). 2012 Mar;220(2):319-30.
[5] Folny V, Raufaste D, Lukovic L, et al. Pancreatic vasopressin V1b receptors: characterization in In-R1-G9 cells and localization in human pancreas. Am J Physiol Endocrinol Metab. 2003 Sep;285(3):E566-76.
[6] Javadian N, Rahimi N, Javadi-Paydar M, et al. The modulatory effect of nitric oxide in pro- and anti-convulsive effects of vasopressin in PTZ-induced seizures threshold in mice. Epilepsy Res. 2016 Oct;126:134-40.
[7] Cheng W, Sun Y, Wu Q, et al. Paraventricular Nucleus P2X7 Receptors Aggravate Acute Myocardial Infarction Injury via ROS-Induced Vasopressin-V1b Activation in Rats. Neurosci Bull. 2021 May;37(5):641-656.
SSR 149415是一种选择性非肽类Vasopressin V1b Receptor拮抗剂[1-2]。SSR 149415主要被用于治疗应激相关障碍（如抑郁症和焦虑症）的相关研究中[3-4]。
在体外，SSR 149415（0.66–1.2nM）预处理In-R1-G9细胞15分钟，随后以精氨酸加压素（AVP；100nM）刺激4–15分钟，显著抑制AVP诱导的细胞内钙离子浓度升高和胰高血糖素分泌，同时拮抗AVP介导的细胞增殖作用[5]。
在体内，SSR 149415（10mg/kg）通过腹腔注射预处理NMRI小鼠，随后注射AVP（20μg/kg），SSR 149415显著逆转AVP的抗惊厥作用[6]。SSR 149415（40ng；0.1μL）通过下丘脑室旁核（PVN）微注射，用于处理急性心肌梗死（AMI）模型大鼠。SSR 149415显著改善了AMI诱导的血流动力学功能障碍和心脏损伤[7]。