Neuropharmacological and neurochemical evaluation of N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n): a novel serotonergic 5-HT3 receptor antagonist for co-morbid antidepressant- and anxiolytic-like potential using traumatic brain injury model in rats.
BACKGROUND
Several preclinical studies have shown that serotonergic 5-HT3 receptor antagonists play an important role in the management of neuropsychiatric disorders, such as depression and anxiety. In the present study the compound "6n" (N-n-propyl-3-ethoxyquinoxaline-2-carboxamide), a novel 5-HT3 receptor antagonist with an optimal log P (2.52) and pA2 (7.6) value was screened for its neuro-pharmacological potential in chronic rodent models of depression and anxiety named traumatic brain injury (TBI).


METHODS
In this model, a 1 cm midline scalp incision was made, and the muscles were retracted to expose the skull. A stainless steel disc (10 mm in diameter and 3 mm in depth) was placed centrally between the lambda and bregma regions. The injury was induced using the impact acceleration model of TBI. Specifically, a 400 g metal weight was dropped from a height of 1 m guided by a straight pipe, onto the metal disc placed over the rat's skull.


RESULTS
The behavioral anomalies of the TBI rats were attenuated by the chronic treatment of compound 6n (1 and 2 mg/kg, p.o.; 14 days) as observed by the modified open field test (ambulation, rearing, and fecal pellet), sucrose consumption test (% sucrose consumption), elevated plus maze [% open arm entries [OAE] and % time spent in open arm (TSOA)], and marble burying test (numbers). In addition, 6n also increased the levels of neurotransmitters (norepinephrine and serotonin) and brain derived neurotrophic factor (BDNF) in TBI rats.


CONCLUSIONS
The result suggests that compound 6n exhibited antidepressant- and anxiolytic-like effects in rodent models of depression and anxiety.
Shvetank
S
Bhatt
Radhakrishnan
R
Mahesh
Ankur
A
Jindal
Thangaraj
T
Devadoss
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000150:complications / Q000188:drug therapy / Q000523:psychology; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D003863:Depression / Q000150:complications / Q000188:drug therapy / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; C000597539:N-n-propyl-3-ethoxyquinoxaline-2-carboxamide; D011810:Quinoxalines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists