| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Hou, Jian Xing, Yanli Zuo, Daiying Wu, Yingliang Tian, Jingwei Meng, Qingguo Yang, Mina |
| Description |
Author Affiliation: Hou J ( School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China); Xing Y ( School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China); Zuo D ( School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.); Wu Y ( School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China. Electronic address: yingliang_1016@163.com.); Tian J ( State key laboratory of Long-acting and Targeting Drug Delivery Technologies (luye Pharma Group Ltd.), Yantai, Shandong 264003, PR China); Meng Q ( State key laboratory of Long-acting and Targeting Drug Delivery Technologies (luye Pharma Group Ltd.), Yantai, Shandong 264003, PR China); Yang M ( State key laboratory of Long-acting and Targeting Drug Delivery Technologies (luye Pharma Group Ltd.), Yantai, Shandong 264003, PR China.) |
| Abstract |
Triple reuptake inhibitors (TRIs) that inhibit the reuptake of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) are being developed as a new class of antidepressants, which is hypothesized to produce more rapid onset and better efficacy than conventional antidepressants in part due to the addition of the DA component. 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)-ethyl]-phenyl benzoate hydrochloride (PA01), a novel compound, potently bound to the human 5-HT, NE, and DA transporters (Ki=105, 644, and 813nM, respectively), and inhibited the reuptake of 5-HT, NE, and DA into recombinant cells (IC50=341, 427, and 753nM, respectively). In vivo, PA01 dose-dependently decreased immobility time in the forced swimming test (FST) in rats, and the tail suspension test (TST) in mice with higher efficacy than desvenlafaxine succinate (DVS), and showed no stimulatory effect on the spontaneous locomotor activity. The anti-immobility effect of PA01 in the TST was significantly prevented by the pretreatment of mice with DL-p-chlorophenylalanine (pCPA, 300mg/kg, an inhibitor of serotonin synthesis), SCH23390 (0.05mg/kg, s.c., dopamine D1 receptor antagonist), and sulpiride (50mg/kg, i.p., dopamine D2 receptor antagonist). PA01 significantly increased head-twitch response induced by 5-hydroxytryptophan (80mg/kg, i.p., a metabolic precursor to serotonin) in rats, potentiated yohimbine (25mg/kg, s.c., a 2-adrenoceptor antagonist) toxicity, and antagonized high dose apomorphine-induced hypothermia in mice. Taken together, these in vitro and in vivo results indicated that PA01 is a novel triple reuptake inhibitor, and exerts an excellent antidepressant activity in the behavioral despair animal models of depression, with more potent antidepressant activity than DVS at the same dose. |
| File Format |
HTM / HTML |
| ISSN |
00319384 |
| Volume Number |
138 |
| e-ISSN |
1873507X |
| Journal |
Physiology & Behavior |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2015-01-01 |
| Publisher Place |
United States |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Research Support, Non-u.s. Gov't Cricetulus Cyclohexanols Species Specificity Humans Male Antidepressive Agents Motor Activity Journal Article Discipline Physiology Dose-response Relationship, Drug Desvenlafaxine Succinate Molecular Structure Physiology Disease Models, Animal Binding, Competitive Dopamine Serotonin Drug Therapy Rats, Sprague-dawley Depression Pharmacology Cho Cells Metabolism Drug Effects Physiopathology Chemistry Animals Neurotransmitter Uptake Inhibitors Mice Norepinephrine Discipline Behavioral Neuroscience Hypothermia |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Experimental and Cognitive Psychology Behavioral Neuroscience |
