Effect of acute and chronic treatment with QCF-3 (4-benzylpiperazin-1-yl) (quinoxalin-2-yl) methanone, a novel 5-HT(3) receptor antagonist, in animal models of depression.
The serotonin type 3 (5-HT(3)) receptor is unique among the seven recognized serotonin receptor "families". The existence serotonin type 3 receptor (5-HT(3)) in neuro-anatomical regions stimulated the research interest for novel therapeutic targets such as anxiety, depression, nociception and cognitive function. In the current study, (4-benzylpiperazin-1-yl) (quinoxalin-2-yl) methanone (QCF-3), a novel 5-HT(3) receptor antagonist, with an optimal log P (the logarithm of the ratio of the concentrations of the un-ionized solute in the solvents is called log P) and significant pA2 value (is a negative logarithm of the molar concentration of antagonist required to reduce the effect of multiple dose agonist to that of single dose) was screened for its anti-depressant potential using rodent behavioral models of depression. Psycho-pharmacological investigations involved acute and chronic treatment (14 days) with QCF-3 and assessment of behavior during the forced swim test (FST) and tail suspension test (TST) in mice and olfactory bulbectomised rats. A dose response study in mice revealed an initial anti-depressant-like effect of QCF-3 (0.5-4 mg/kg, ip) in the FST and TST. Interaction studies showed that QCF-3 (1 and 2 mg/kg) significantly enhanced the antidepressant action of fluoxetine and bupropion in the FST and TST, respectively. QCF-3 (1 and 2 mg/kg) potentiated the 5-hydroxytryptophan (5-HTP) induced head twitches response in mice and reversed reserpine-induced hypothermia in rats. Further, OBX rats exhibited behavioral anomalies in the open field and hyper-emotionality tests that were attenuated by chronic QCF-3 treatment. In conclusion, this behavioral study describes an antidepressant-like effect of QCF-3 in rodent behavioral models of depression.
Devadoss
Thangaraj
T
Pharmacy Group, FD-III, Birla Institute of Technology & Science, Pilani, Rajasthan-333031, India.
Pandey
Dilip K
DK
Mahesh
Radhakrishnan
R
Yadav
Shushil K
SK
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009830:Olfactory Bulb / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*
C552308:(4-benzylpiperazin-1-yl)(quinoxalin-2-yl)methanone; D000928:Antidepressive Agents; D010879:Piperazines; D011810:Quinoxalines; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D006916:5-Hydroxytryptophan