Central and peripheral analgesic action of non-acidic non-steroidal anti-inflammatory drugs in mice and rats.

The site of the analgesic action of non-acidic (basic), non-steroidal anti-inflammatory drugs (NSAIDs) was investigated in the acetic acid writhing test. In rats the anti-writhing potency ratio of i.p. to i.v. administered aminopyrine, tiaramide HCl or mepirizole was 4.96, 1.87 and approximately 4, respectively, suggesting an involvement of both central and peripheral mechanisms of their anti-writhing action. In mice the ratio of intracisternally (i.c.) to i.v. administered aminopyrine, tiaramide HCl or mepirizole was approximately 5.8, approximately 50 and approximately 7, respectively. Since the above ratio for morphine and methadone was higher than 10 and tolmetin sodium, an acidic NSAID, did not produce any anti-writhing effect when given i.c., it could be assumed that the anti-writhing action of these non-acidic NSAIDs was at least partially mediated via the central nervous system. In common with tolmetin sodium, aminopyrine showed more of anti-inflammatory potency when administered i.p. than i.v. and it did not reduce vascular permeability in mice when administered i.c. These results suggest that non-acidic NSAIDs produce their anti-writhing action through both central and peripheral mechanisms.