title: Anti-depressant-like activity of a novel serotonin type-3 (5-HT3) receptor antagonist in rodent models of depression.
abstract: N-Cyclohexyl-3-methoxyquinoxalin-2-carboxamide (QCM-13), a novel 5-HT3 antagonist identified from a series of compounds with higher pA2 (7.6) and good log P (2.91) value was screened in rodent models of depression such as forced swim test (FST), tail suspension test (TST), interaction studies with standard anti-depressants and confirmatory studies such as reversal of parthenolide induced depression and reserpine induced hypothermia. In FST (2 and 4 mg/kg) and TST (2 and 4 mg/kg), QCM-13 significantly reduced the duration of immobility in mice without affecting the base line locomotion. QCM-13 (2 and 4 mg/kg) was also found to have significant interaction with standard anti-depressants (fluoxetine and bupropion in FST and TST respectively). Further, reversal of parthenolide induced depression in mice and reserpine induced hypothermia in rat models indicate the serotonergic influence of QCM-13 for anti-depressant potential.
authors.affiliation: Department of Pharmacy, FD-III, Birla Institute of Technology & Science (BITS), Pilani, 333 031, India. deepaligupta2010@gmail.com
authors.forename: Deepali
authors.initials: D
authors.lastname: Gupta
authors.forename: Thangaraj
authors.initials: T
authors.lastname: Devadoss
authors.forename: Shvetank
authors.initials: S
authors.lastname: Bhatt
authors.forename: Baldev
authors.initials: B
authors.lastname: Gautam
authors.forename: Ankur
authors.initials: A
authors.lastname: Jindal
authors.forename: Dilip
authors.initials: D
authors.lastname: Pandey
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahesh
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; C561327:N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide; D011810:Quinoxalines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists