title: 2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carboxylic acids: novel 5-HT3 receptor antagonists with anxiolytic-like activity in rodent behavioral models.
abstract: The aim of this study was to investigate the anxiolytic potential of a series of novel carboxylic acid based 1,8 naphthyridines as 5-HT3 receptor antagonists. The pA2 values of all the compounds were determined against agonist 2-methyl-5-hydroxytryptamine in longitudinal muscle myenteric plexus preparations from guinea pig ileum. Compounds with higher pA2 values, particularly those greater than ondansetron, a standard 5-HT3 receptor antagonist, and optimal log P values were screened in mice by using behavioral tests such as a light-dark (L/D) aversion test, elevated plus maze (EPM) test, and an open field test (OFT). In the L/D test, compounds 7a, 7b, 7d, 7e, and 7i (2 mg/kg body mass, intraperitoneal) significantly (P < 0.05) increased the latency time to leave the light compartment, total time spent in the light compartment, and the number of transitions between the light and dark compartments. Compounds 7a, 7d, 7f, 7h, and 7i (2 mg/kg, i.p.) significantly (P < 0.05) increased the time spent in the open arms and the number of entries into the open arms in the EPM test. In addition, compounds 7a, 7d, 7e, 7f, and 7h (2 mg/kg, i.p.) significantly (P < 0.05) increased the ambulation scores and the frequency of rearing in the OFT.
authors.affiliation: Department of Pharmacy, FD-III, Birla Institute of Technology & Science, Pilani, Rajasthan 333 031, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahesh
authors.forename: Arghya Kusum
authors.initials: AK
authors.lastname: Dhar
authors.forename: Ankur
authors.initials: A
authors.lastname: Jindal
authors.forename: Shvetank
authors.initials: S
authors.lastname: Bhatt
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D009287:Naphthyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D017294:Ondansetron / Q000494:pharmacology; D011930:Reaction Time; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects* / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D002264:Carboxylic Acids; D009287:Naphthyridines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D017294:Ondansetron