| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Chaki, Shigeyuki Shimazaki, Toshiharu Nishiguchi, Mariko Funakoshi, Takeo Iijima, Michihiko Ito, Akie Kanuma, Kosuke Sekiguchi, Yoshinori |
| Description |
Author Affiliation: Chaki S ( Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan. Electronic address: s-chaki@so.taisho.co.jp.); Shimazaki T ( Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.); Nishiguchi M ( Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.); Funakoshi T ( Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.); Iijima M ( Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.); Ito A ( Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.); Kanuma K ( Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.); Sekiguchi Y ( Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.) |
| Abstract |
Melanin-concentrating hormone receptor 1 (MCH1 receptor) is known to be involved in the control of mood and stress, in addition to the regulation of feeding. Here, we report further evidence that the blockade of the MCH1 receptor exhibits antidepressant and anxiolytic-like effects in a variety of animal models using TASP0382650 and TASP0489838, newly synthesized MCH1 receptor antagonists, with different scaffolds. Both TASP0382650 and TASP0489838 exhibited high affinities for human MCH1 receptor with IC50 values of 7.13 and 3.80nM, respectively. Both compounds showed potent antagonist activities at the MCH1 receptor, as assessed using MCH-increased [(35)S]GTPγS binding to human MCH1 receptor and an MCH-induced [Ca(2+)]i assay in rat MCH1 receptor expressing cells. In contrast, neither TASP0382650 nor TASP0489838 showed an affinity for the MCH2 receptor, another MCH receptor subtype. The oral administration of TASP0382650 or TASP0489838 significantly reduced the immobility time during the forced swimming test in rats, and reduced hyperemotionality induced by an olfactory bulbectomy, both of which are indicative of an antidepressant-like potential. In the olfactory bulbectomy model, the antidepressant effect of TASP0382650 appeared following a single administration, suggesting a faster onset of action, compared with current medications. Moreover, both TASP0382650 and TASP0489838 exhibited anxiolytic effects in several animal models of anxiety. In contrast, both TASP0382650 and TASP0489838 did not affect spontaneous locomotor activity, motor function, spatial memory during the Morris water maze task, or the convulsion threshold to pentylenetetrazole. These findings provide additional evidence that the blockade of the MCH1 receptor exhibits antidepressant- and anxiolytic activities with no adverse effects in experimental animal models. |
| File Format |
HTM / HTML |
| ISSN |
00913057 |
| Volume Number |
135 |
| e-ISSN |
18735177 |
| Journal |
Pharmacology Biochemistry and Behavior |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2015-08-01 |
| Publisher Place |
United States |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Behavioral Sciences Discipline Biochemistry Discipline Pharmacology Anti-anxiety Agents Adverse Effects Pharmacology Antidepressive Agents Receptors, Somatostatin Antagonists & Inhibitors Animals Anticonvulsants Behavior, Animal Drug Effects Emotions Guanosine 5'-o-(3-thiotriphosphate) Metabolism Humans Male Maze Learning Mice Mice, Inbred Icr Motor Activity Olfactory Bulb Physiology Rats Rats, Sprague-dawley Rats, Wistar Swimming Psychology Journal Article |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Biological Psychiatry Behavioral Neuroscience Biochemistry Clinical Biochemistry Toxicology Pharmacology |
