GW117: A novel serotonin (5-HT2C) receptor antagonist and melatonin (MT1/MT2) receptor agonist with potential antidepressant-like activity in rodents

被引：10
|
作者：
Gao, Nana [1 ]
Zheng, Wei [2 ]
Murezati, Tiliwaerde [2 ]
Gu, Wei [3 ]
Li, Xiaorong [2 ]
Jin, Zengliang [2 ]
机构：
[1] Captial Med Univ, Beijing Shijitan Hosp, Dept Gastrointestinal Surg & Clin Nutr, Beijing, Peoples R China
[2] Capital Med Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100069, Peoples R China
[3] Beijing Guangwei Pharmaceut Technol Co Ltd, Beijing, Peoples R China
来源：
CNS NEUROSCIENCE & THERAPEUTICS | 2021年 / 27卷 / 06期
基金：
中国国家自然科学基金;
关键词：
5‐ HT2C receptor; antidepressant; GW117; melatonin receptor; REUPTAKE INHIBITORS; AGOMELATINE; NOREPINEPHRINE; DRUGS; MODEL; DEPRESSION; STRESS; RATS;
D O I：
10.1111/cns.13630
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Aims To evaluate the antidepressant-like effect of compound GW117 in rodents using in vitro binding and uptake assays as well in vivo behavioral tests. Methods We investigated the target profile of GW117 using [S-35]-GTP gamma S and [H-3]PIP binding. Using the forced swimming test and chronic unpredictable stress in rats, tail suspension test in mice and rats, and learned helplessness model in mice, we further revealed the antidepressant-like and anxiolytic-like effects of GW117. Results The current study suggests that GW117 displays serotonin 2C (5-HT2C) receptor antagonist and melatonin type 1 and 2 (MT1/MT2) receptor agonist properties, as well as evident antidepressant and anxiolytic effects. Conclusion These data suggest that GW117 is probably a potent antidepressant.
引用
收藏
页码：702 / 713
页数：12
相关论文
共 50 条
  • [31] Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist
    Kato, K
    Hirai, K
    Nishiyama, K
    Uchikawa, O
    Fukatsu, K
    Ohkawa, S
    Kawamata, Y
    Hinuma, S
    Miyamoto, M
    NEUROPHARMACOLOGY, 2005, 48 (02) : 301 - 310
  • [32] Safety profile of tasimelteon, a melatonin MT1 and MT2 receptor agonist: pooled safety analyses from six clinical studies
    Leger, Damien
    Quera-Salva, Maria-Antonia
    Vecchierini, Marie-Francoise
    Ogrizek, Pascale
    Perry, Christina A.
    Dressman, Marlene A.
    EXPERT OPINION ON DRUG SAFETY, 2015, 14 (11) : 1673 - 1685
  • [33] Antidepressant-like effects of the 5-HT2C selective agonist WAY-909 in rodents
    Rosenzweig-Lipson, S.
    Sabb, A.
    Malberg, J.
    Brennan, J.
    Piesla, M.
    Grauer, S.
    Marquis, K.
    Mitchell, P.
    Lucki, I.
    FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2004, 18 : 143 - 143
  • [34] Decreased MT1 and MT2 melatonin receptor expression in extrapineal tissues of the rat during physiological aging
    Sanchez-Hidalgo, Marina
    Guerrero Montavez, Juan Miguel
    Carrascosa-Salmoral, Maria del Pilar
    Naranjo Gutierrez, Maria del Carmen
    Lardone, Patricia Judith
    de la Lastra Romero, Catalina Alarcon
    JOURNAL OF PINEAL RESEARCH, 2009, 46 (01) : 29 - 35
  • [35] 4D-QSAR study of melatonin receptor ligands for MT1 and MT2 receptors.
    Esposito, EX
    Madura, JD
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 222 : U403 - U404
  • [36] Ramelteon, a selective MT1/MT2 receptor agonist, suppresses the proliferation and invasiveness of endometrial cancer cells
    Kiyono Osanai
    Yoichi Kobayashi
    Masahiro Otsu
    Tomoko Izawa
    Keiji Sakai
    Mitsutoshi Iwashita
    Human Cell, 2017, 30 : 209 - 215
  • [37] Ramelteon, a selective MT1/MT2 receptor agonist, suppresses the proliferation and invasiveness of endometrial cancer cells
    Osanai, Kiyono
    Kobayashi, Yoichi
    Otsu, Masahiro
    Izawa, Tomoko
    Sakai, Keiji
    Iwashita, Mitsutoshi
    HUMAN CELL, 2017, 30 (03): : 209 - 215
  • [38] MT1 AND MT2 MELATONIN RECEPTOR EXPRESSION AND IN VITRO MELATONIN EFFECT ON THE PHA-DEPENDENT ACTIVATION OF HUMAN PBMC
    Georgiev, Georgi N.
    Mourdjeva, Milena
    Oreshkova, Tsvetelina
    Pankov, Roumen
    Konakchieva, Rossitza
    COMPTES RENDUS DE L ACADEMIE BULGARE DES SCIENCES, 2019, 72 (11): : 1500 - 1506
  • [39] Effect of multiple oral doses of venlafaxine on the systemic availability of ramelteon, an MT1/MT2 receptor agonist
    Karim, A.
    Bradford, D.
    Zhao, Z.
    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2006, 9 : S138 - S138
  • [40] Distinct role of melatonin MT1 and MT2 receptors in sleep and anxiety: insights from melatonin receptor knockout mice
    Comai, S.
    Ochoa-Sanchez, R.
    Gobbi, G.
    EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2014, 24 : S268 - S268
12345