RESUMEN
In this study, twenty-two new [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (5a-n, 6a-h) were synthesized under microwave irradiation (MWI). The chemical structures of the compounds were elucidated by their IR, 1H-NMR, LC-MS, and elemental analysis. The compounds were tested for antinociceptive activity by using the tail clip, tail flick, hot plate, and writhing methods in mice. The varying levels of antinociceptive activity of the compounds were compared with those of aspirin. Among these compounds, compound 5g and 5j were found to be significantly more active than the other compounds and the standard in the tests. Also, inhibitory effects of the test compounds on COX-1 and COX-2 activities were investigated. DuP-697 for COX-2 and SC-560 for COX-1 were used as reference standards.
RESUMEN
Background & objectives: Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether gabapentin has analgesic effects in mice and rats. Methods: The mice were divided into 10 groups (n=7) with various treatments to assess central and peripheral antinociceptive activity of gabapentin. Hot plate, tail clip and tail flick tests were applied for the investigation of central antinociceptive activity and the writhing test was applied for the investigation of peripheral antinociceptive activity. In addition, we also evaluated the levels of PGE2 and nNOS on perfused hippocampus slices of rats. Results: Gabapentin showed a peripheral antinociceptive effect at all doses and a central antinociceptive effect at 30mg/kg dose. While the L-NAME and cyproheptadine changed the central and peripheral effects of gabapentin, naloxone did not change these effects. In vitro studies showed that gabapentin significantly increased nNOS level. PGE2 and nNOS were found to have an important role in the antinociceptive effects of gabapentin at all doses and its combinations with L-NAME, cyproheptadine, indomethacine, and naloxone. As expected, PGE2 levels decreased in all groups, while nNOS levels increased, which is believed to be an adaptation mechanism. Interpretation & conclusions: Our findings indicate that arachidonate, nitrergic and serotonergic systems play an important role in the antinociceptive activity of gabapentin except for the opioidergic system. Additionally, this effect occured centrally and peripherally. These effects were also mediated by nNOS and PGE2.