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

被引：11

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

页码：702 / 713

页数：12

共 50 条

[31] 5-HT2A receptor inactivation potentiates the acute antidepressant-like activity of escitalopram: involvement of the noradrenergic system [J].

Quesseveur, G. ;

Reperant, C. ;

David, D. J. ;

Gardier, A. M. ;

Sanchez, C. ;

Guiard, B. P. .

EXPERIMENTAL BRAIN RESEARCH, 2013, 226 (02) :285-295

[32] 5-HT2A receptor inactivation potentiates the acute antidepressant-like activity of escitalopram: involvement of the noradrenergic system [J].

G. Quesseveur ;

C. Repérant ;

D. J. David ;

A. M. Gardier ;

C. Sanchez ;

B. P. Guiard .

Experimental Brain Research, 2013, 226 :285-295

[33] Antidepressant-like activity of (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a), a novel 5-HT 3 receptor antagonist: An investigation in behaviour-based rodent models of depression [J].

Mahesh, Radhakrishnan ;

Kumar, Baldev ;

Jindal, Ankur ;

Bhatt, Shvetank ;

Devadoss, Thangaraj ;

Pandey, Dilip Kumar .

INDIAN JOURNAL OF PHARMACOLOGY, 2012, 44 (05) :560-565

[34] Antidepressant-like effect of novel 5-HT3 receptor antagonist N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p): An approach using rodent behavioral antidepressant tests [J].

Bhatt, Shvetank ;

Mahesh, Radhakrishnan ;

Devadoss, Thangaraj ;

Jindal, Ankur Kumar .

INDIAN JOURNAL OF PHARMACOLOGY, 2013, 45 (04) :348-353

[35] Piperazine Analogs of Naphthyridine-3-carboxamides and Indole-2-carboxamides: Novel 5-HT3 Receptor Antagonists with Antidepressant-Like Activity [J].

Dhar, Arghya K. ;

Mahesh, Radhakrishnan ;

Jindal, Ankur ;

Bhatt, Shvetank .

ARCHIV DER PHARMAZIE, 2015, 348 (01) :34-45

[36] The selective 5-HT2A receptor antagonist M100907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine [J].

Marek, GJ ;

Martin-Ruiz, R ;

Abo, A ;

Artigas, F .

NEUROPSYCHOPHARMACOLOGY, 2005, 30 (12) :2205-2215

[37] Pharmacological profile of the 5-HT2c receptor agonist WAY-163909;: Therapeutic potential in multiple indications [J].

Dunlop, John ;

Marquis, Karen L. ;

Lim, H. K. ;

Leung, Louis ;

Kao, John ;

Cheesman, Cynthia ;

Rosenzweig-Lipson, Sharon .

CNS DRUG REVIEWS, 2006, 12 (3-4) :167-177

[38] The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine [J].

Gerard J Marek ;

Raul Martin-Ruiz ;

Allyson Abo ;

Francesc Artigas .

Neuropsychopharmacology, 2005, 30 :2205-2215

[39] Melatonin MT1/2 receptor stimulation reduces cortical overflow of cholecystokinin-like material in a model of anticipation of social defeat in the rat [J].

Becker, C ;

Andre, J ;

Zeau, B ;

Rettori, MC ;

Guardiola-Lemaitre, B ;

Hamon, M ;

Benoliel, JJ .

NEUROPHARMACOLOGY, 2004, 46 (08) :1158-1167

[40] A novel 5-HT2A receptor antagonist exhibits antidepressant-like effects in a battery of rodent behavioural assays: Approaching early-onset antidepressants [J].

Pandey, Dilip Kumar ;

Mahesh, Radhakrishnan ;

Kumar, Akutota Ashok ;

Rao, V. Sambasiva ;

Arjun, Muralidharan ;

Rajkumar, Ramamoorthy .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2010, 94 (03) :363-373

← 1 2 3 4 5 →