title: Design, synthesis and evaluation of antidepressant activity of novel 2-methoxy 1, 8 naphthyridine 3-carboxamides as 5-HT3 receptor antagonists.
abstract: A series of novel 1,8-naphthyridine-3-carboxamides as 5-HT3 receptor antagonists were synthesized with an intention to explore the antidepressant activity of these compounds. The title carboxamides were designed using ligand-based approach keeping in consideration the structural requirement of the pharmacophore of 5-HT3 receptor antagonists. The compounds were synthesized using appropriate synthetic route from the starting material nicotinamide. 5-HT3 receptor antagonism of all the compounds, which was denoted in the form of pA2 value, was determined in longitudinal muscle myenteric plexus preparation from guinea-pig ileum against 5-HT3 agonist, 2-methyl-5-HT. Compound 8g (2-methoxy-1, 8-naphthyridin-3-yl) (2-methoxy phenyl piperazine-1-yl) methanone was identified as the most active compound, which expressed a pA2 value of 7.67. The antidepressant activity of all the compounds was examined in mice model of forced swim test (FST); importantly, none of the compounds was found to cause any significant changes in the locomotor activity of mice at the tested dose levels. In FST, the compounds with considerably higher pA2 value exhibited promising antidepressant-like activity, whereas compounds with lower pA2 value did not show antidepressant-like activity as compared to the control group.
authors: Department of Pharmacy, FD-III, Birla Institute of Technology & Science, Pilani, Rajasthan, 333 031, India.
authors: Radhakrishnan
authors: R
authors: Mahesh
authors: Arghya Kusum
authors: AK
authors: Dhar
authors: Ankur
authors: A
authors: Jindal
authors: Shvetank
authors: S
authors: Bhatt
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D015195:Drug Design; D006168:Guinea Pigs; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D009287:Naphthyridines / Q000737:chemistry*; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry* / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D000928:Antidepressive Agents; D009287:Naphthyridines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists
keywords: 1,8 naphthyridine 3-carboxamides; 5-HT3 receptor antagonist; antidepressant; forced swim test; spontaneous locomotor activity