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Design, Synthesis, and Pharmacological Evaluation of Novel 2‐(4‐substituted piperazin‐1‐yl)1, 8 Naphthyridine 3‐Carboxylic Acids as 5‐ HT 3 Receptor Antagonists for the Management of Depression
Author(s) -
Dhar Arghya K.,
Mahesh Radhakrishnan,
Jindal Ankur,
Devadoss Thangaraj,
Bhatt Shvetank
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12370
Subject(s) - antagonism , behavioural despair test , tail suspension test , chemistry , myenteric plexus , agonist , pharmacology , receptor , 5 ht receptor , antidepressant , ileum , carboxylic acid , serotonin , medicine , biochemistry , immunohistochemistry , hippocampus
1, 8‐naphthyridine‐3‐carboxylic acid analogs were synthesized and found to possess potential 5‐HT 3 receptor antagonism as well as antidepressant‐like activity. Initially, 5‐HT 3 receptor antagonism of all the compounds was determined in the form of p A 2 value against agonist 2‐methyl 5‐HT in longitudinal muscle–myenteric plexus preparation from guinea‐pig ileum. Among all the compounds tested, compound 7a demonstrated most promising pA 2 value of 7.6. Subsequently, all the compounds were evaluated for antidepressant activity using forced swim test and tail suspension test in mice. Compounds 7a , 7d , 7f , 7h , and 7i exhibited significant (p < 0.05) antidepressant‐like activity as compound to vehicle‐treated group. Importantly, none of the tested compound affected locomotor activity of mice at tested dose levels.